Merge pull request #33 from lshift/update_wording

Update wording of home page and help files

content/help.md

@@ -1,52 +1,41 @@
 # Searching
 
-Variants are identified using [HGVS nomenclature](http://www.hgvs.org/mutnomen/), a standard created by the Human Genome Variation Society.  Most genetic test results are reported in HGVS nomenclature. This nomenclature describes a variant by indicating (1) a reference sequence, (2) what kind of sequence it is (genomic, cDNA or protein), (3) the position of the variant in relation this reference sequence, and (4) the nucloetide or protein differences between the variant and the reference sequence.  For example, _NM_007294.3:c.5053A>G_ indicates a variant relative to reference sequence _NM_007294.3_, which is a cDNA sequence (as indicated by _c_), that the variant is in position 5053, and that it involves changing an _A_ to a _G_.  
+To search just start typing a variant in the search box and it will auto complete. Variants are identified using [HGVS nomenclature](http://www.hgvs.org/mutnomen/), a standard created by the Human Genome Variation Society.  Most genetic test results are reported in HGVS nomenclature. This nomenclature describes a variant by indicating (1) a reference sequence, (2) what kind of sequence it is (genomic, cDNA or protein), (3) the position of the variant in relation this reference sequence, and (4) the nucloetide or protein differences between the variant and the reference sequence.  For example, _NM_007294.3:c.5053A>G_ indicates a variant relative to reference sequence _NM_007294.3_, which is a cDNA sequence (as indicated by _c_), that the variant is in position 5053, and that it involves changing an _A_ to a _G_.
 
 # Table Columns
 
 #### Gene
 
 The Gene column displays the name of the gene on which the variant was found.  This will be either BRCA1 or BRCA2.
 
-#### HGVS cDNA
 
-Nucleotide change expressed according to nomenclature used by [BIC](http://research.nhgri.nih.gov/bic/), namely using nucleotide numbering from nucleotide 1 of the full gene sequence (Genbank: U14680/ BRCA1; U43746/ BRCA2) not the ATG initiator codon, and without renaming of the BRCA1 185del AG and the BRCA1 5382insC mutations, following the universal use of the incorrect base numbers in the literature.  For example, _c.15A>G_ indicates a change of _A_ to _G_ in nucleotide position 15.
+#### Genomic (GRCh38)
+Coordinate of the variant on the GRCh38 reference genome
 
-#### HGVS Protein
+#### Nucleotide
+HGVS string that represents the variant at cDNA nucleotide level
 
+#### Protein
 The protein-level change (if any) that would be introduced by this variant.  HGVS notation indicates the position of the variant within the reference protein sequence, and the change that would be introduced by this variant.  For example, _p.(Tyr15His)_ indicates a change of _Tyr_ (Tyrosine) to _His_ (Histidine) at amino acid 15.  The notation _p.?_ indicates a variant is not within the protein-coding portions of the gene.
 
-#### BIC Nucleotide
-
-Nucleotide change expressed according to nomenclature used by BIC ([http://research.nhgri.nih.gov/bic/](http://research.nhgri.nih.gov/bic/)), namely using nucleotide numbering from the first nucleotide of the full gene sequence, in contrast to HGVS notation which begins numbering relative to the start of the protein-coding portion of the sequence. 
-
-#### BIC Protein
-
-Protein amino acid change expressed according to nomenclature used by BIC ([http://research.nhgri.nih.gov/bic/](http://research.nhgri.nih.gov/bic/)).  When this column is blank, it indicates that the variant is not in a protein-coding position within the gene. 
-
-#### Genomic Coordinate
-
-Position of the variant in the reference genome, relative to the positive DNA strand.
-
-
 #### Pathogenicity
-The Pathogenicity column indicates whether expert curators have determined if the variant is pathogenic or benign. 
+The Pathogenicity column indicates whether expert curators have determined if the variant is pathogenic or benign.
 
-##### What do these classifications mean?
-- *Pathogenic variants* confer an increased risk of disease. 
+##### _What do these classifications mean?_
+- *Pathogenic variants* confer an increased risk of disease.
 - *Likely pathogenic variants* have good evidence to support an association with disease risk.
 - *Likely benign variants* have good evidence to support no association with disease risk.
 - *Benign variants* are not associated with any markedly increased risk of disease.
 - *Variants of uncertain significance (VUS)* are those for which the evidence of disease risk is not clear yet, sometimes because there is not yet enough evidence to classify them as either pathogenic or benign.
 
-##### My variant is classified pathogenic. What do I do now?
+##### _My variant is classified pathogenic. What do I do now?_
 This website is not intended to provide a clinical diagnosis. Please contact your primary care provider to determine what steps may be necessary.
 
-#### Source
 
-The variants shown on this site are stored in larger genomic variant databases.  One major variant datase is [ClinVar](http://www.ncbi.nlm.nih.gov/clinvar/).  This column gives the variant's ID in the ClinVar database, and contains hyperlinks showing the variant in ClinVar.
+#### Source URL(s)
+URL(s) pointing back to the original source data
+
 
-
 # Variant Detail Page Glossary
 
 #### Gene symbol

content/help_research.md

@@ -1,52 +1,219 @@
-Placeholder for research mode help page
-
 # Searching
 
-Variants are identified using [HGVS nomenclature](http://www.hgvs.org/mutnomen/), a standard created by the Human Genome Variation Society.  Most genetic test results are reported in HGVS nomenclature. This nomenclature describes a variant by indicating (1) a reference sequence, (2) what kind of sequence it is (genomic, cDNA or protein), (3) the position of the variant in relation this reference sequence, and (4) the nucloetide or protein differences between the variant and the reference sequence.  For example, _NM_007294.3:c.5053A>G_ indicates a variant relative to reference sequence _NM_007294.3_, which is a cDNA sequence (as indicated by _c_), that the variant is in position 5053, and that it involves changing an _A_ to a _G_.  
+To search just start typing a variant in the search box and it will auto complete. Variants are identified using [HGVS nomenclature](http://www.hgvs.org/mutnomen/), a standard created by the Human Genome Variation Society.  Most genetic test results are reported in HGVS nomenclature. This nomenclature describes a variant by indicating (1) a reference sequence, (2) what kind of sequence it is (genomic, cDNA or protein), (3) the position of the variant in relation this reference sequence, and (4) the nucloetide or protein differences between the variant and the reference sequence.  For example, _NM_007294.3:c.5053A>G_ indicates a variant relative to reference sequence _NM_007294.3_, which is a cDNA sequence (as indicated by _c_), that the variant is in position 5053, and that it involves changing an _A_ to a _G_.
 
 # Table Columns
 
-#### Gene
+#### Mutation category (BIC)
 
-The Gene column displays the name of the gene on which the variant was found.  This will be either BRCA1 or BRCA2.
+Transcript context of the mutation.
 
-#### HGVS cDNA
+#### PolyPhen score
 
-Nucleotide change expressed according to nomenclature used by [BIC](http://research.nhgri.nih.gov/bic/), namely using nucleotide numbering from nucleotide 1 of the full gene sequence (Genbank: U14680/ BRCA1; U43746/ BRCA2) not the ATG initiator codon, and without renaming of the BRCA1 185del AG and the BRCA1 5382insC mutations, following the universal use of the incorrect base numbers in the literature.  For example, _c.15A>G_ indicates a change of _A_ to _G_ in nucleotide position 15.
+PolyPhen score.  A score closer to 1 suggests a damaging variant
 
-#### HGVS Protein
+#### SIFT score
 
-The protein-level change (if any) that would be introduced by this variant.  HGVS notation indicates the position of the variant within the reference protein sequence, and the change that would be introduced by this variant.  For example, _p.(Tyr15His)_ indicates a change of _Tyr_ (Tyrosine) to _His_ (Histidine) at amino acid 15.  The notation _p.?_ indicates a variant is not within the protein-coding portions of the gene.
+SIFT score, indicating if the variant is tolerated, deleterious or other
 
-#### BIC Nucleotide
+#### African Allele Frequency (1000 Genomes)
 
-Nucleotide change expressed according to nomenclature used by BIC ([http://research.nhgri.nih.gov/bic/](http://research.nhgri.nih.gov/bic/)), namely using nucleotide numbering from the first nucleotide of the full gene sequence, in contrast to HGVS notation which begins numbering relative to the start of the protein-coding portion of the sequence. 
+African-American minor allele frequency, from 1000 Genomes
 
-#### BIC Protein
+#### Allele Frequency
 
-Protein amino acid change expressed according to nomenclature used by BIC ([http://research.nhgri.nih.gov/bic/](http://research.nhgri.nih.gov/bic/)).  When this column is blank, it indicates that the variant is not in a protein-coding position within the gene. 
+Allele frequency, estimated from the combination of ExAC, ESP and 1000 Genomes allele frequences
 
-#### Genomic Coordinate
+#### Allele Frequency (1000 Genomes)
+
+Overall allele frequency, from 1000 Genomes
+
+#### Allele Frequency (ExAC)
+
+Minor allele frequency
+
+#### AMR Allele Frequency (1000 Genomes)
+
+Allele frequency in the Admixed American population, from 1000 Genomes
+
+#### EAS Allele Frequency (1000 Genomes)
+
+Allele frequency in the East Asian population, from 1000 Genomes
+
+#### EUR Allele Frequency (1000 Genomes)
+
+European allele frequency in the European population, from 1000 Genomes
+
+#### Maximum Allele Frequency
+Highest allele frequency reported by any data source, for any population.
+
+#### Allele Frequencies: EA|AA|All (ESP)
+Allele frequencies from ESP, expressed as EA (European)|AA (African American)|All
+
+#### SAS Allele Frequency (1000 Genomes)
+Allele frequency in the Southeast Asian population, from 1000 Genomes
+
+#### Variant Frequency (LOVD)
+Allele frequency, from LOVD, expressed as a fraction relative to the reference population
+
+#### BIC Variant Identifier
+Variant identifier in BIC nomenclature
+
+#### Protein
+HGVS protein identifier
+
+#### SCV Accession (ClinVar)
+SCV accession in the ClinVar repository
+
+#### Nucleotide
+HGVS string that represents the variant at cDNA nucleotide level
+
+#### Other HGVS Nucleotide(s)
+Other HGVS cDNA strings observed for this variant
+
+#### Protein Amino Acid Change
+Amino acid change, in single-letter amino acid format and protein position
+
+#### Reference cDNA Sequence
+Sequence on which the variant was observed
+
+#### Gene Symbol
+Gene that the variant maps to (BRCA1 or BRCA2).
+
+#### Genomic (GRCh38)
+Coordinate of the variant on the GRCh38 reference genome
+
+#### Genomic (GRCh36)
+Coordinate of the variant on the GRCh36 reference genome
+
+#### Genomic (GRCh37)
+Coordinate of the variant on the GRCh37 reference genome
+
+#### Allele Origin (ClinVar)
+Allele origin, indicating if the variant is germline or somatic in origin.  From ClinVar.
+
+####  Allele Origin (ENIGMA)
+Allele origin, indicating if the variant is germline or somatic in origin.  From ENIGMA.
+
+####  Ethnicity (BIC)
+Ethnicities of the observed patients, from BIC
+
+#### Allele Origin (BIC)
+Origin of the allele, Germline (G) or Somatic (S).  From BIC
 
-Position of the variant in the reference genome, relative to the positive DNA strand.
+#### Allele Origin (LOVD)
+Allele origin, from LOVD
 
+#### Patient Nationality (BIC)
+Nationality of the patient associated with the variant.  From BIC
+
+#### Variant Haplotype (BIC)
+Haplotype (example: FA FANCD1_00037)
+
+#### Family members carrying this variant (BIC)
+Number of family members carrying this variant.  From BIC.
+
+#### Co-occurrence likelihood (exLOVD)
+The likelihood ratio based on the frequency of co-occurrence between the variant of interest and clearly
+ pathogenic variants in the same gene. From exLOVD.
+
+#### Prior probability of pathogenicity (exLOVD)
+The combined prior probability in favor of pathogenicity. is a combination of the missense analysis prior
+ probability and the splicing analysis prior probability. Generally, it is the higher of these two prior probabilities.  From exLOVD.
+
+#### Missense analysis probability of pathogenicity (exLOVD)
+This prior probability estimate combines position in the protein with an evaluation of missense substitutions
+ that fall in the proteins key functional domains.  From exLOVD.
+
+#### Probability of pathogenicity (exLOVD)
+Posterior probability of pathogenicity. From exLOVD.
+
+#### Segregation Likelihood Ratio (exLOVD)
+The likelihood ratio based on segregation analysis
+
+#### Summary Family History Likelihood Ratio (exLOVD)
+The likelihood ratio based on an analysis of the severity of summary family histories of breast and/ or ovarian
+ cancer.
+
+#### Assertion Method (ENIGMA)
+URL of the ENIGMA classification rules
+
+#### Clinical Significance Citation (ENIGMA)
+Pubmed ID on this clinical significance
+
+#### Literature Reference (BIC)
+Literature Reference(s).  From BIC
+
+#### Literature Reference (exLOVD)
+Literature Reference(s).  From exLOVD.
+
+#### Assertion Method (ENIGMA)
+Basis of the evaluation (ENIGMA variants , invariant)
+
+#### Clinical Significance (BIC)
+Clinical significance, from BIC.  This ranges from Class 1 to Class 5, where Class 1 is Benign and Class 5 is
+ Pathogenic.
+
+#### Clinical Importance (BIC)
+Clinical significance (yes|no|pending|unknown)
+
+#### Clinical Significance (ClinVar)
+Clinical significance according to ClinVar
+
+#### Clinical Significance (ENIGMA)
+Clinical significance according to ENIGMA
+
+#### Collection Method (ENIGMA)
+Method by which ENIGMA arrives at its clinical classificaitons
+
+#### Comment on Clinical Significance (ENIGMA)
+Comment on how the derivation of the IARC class, from ENIGMA
+
+#### Date last evaluated (ENIGMA)
+Date at which the variant was evaluated by ENIGMA
+
+#### Date last updated (ClinVar)
+Date the variant was last updated in ClinVar
+
+#### Has Discordant Evidence
+Indicates if there is evidence of a discordant classification for this variant
+
+#### Functional Analysis Result (LOVD)
+Functional analysis or prediction of the impact of this variant.  From LOVD
+
+#### Functional Analysis Method (LOVD)
+The method used in analyzing variant function.  From LOVD.
+
+#### Analysis Method (ClinVar)
+Method by which the significance of the variant was determined.  From ClinVar
 
 #### Pathogenicity
-The Pathogenicity column indicates whether expert curators have determined if the variant is pathogenic or benign. 
+Pathogenicity, as reported by ENIGMA, ClinVar and BIC.
+
+#### ClinVar Accession
+ClinVar SCV accession
+
+#### Condition Category (ENIGMA)
+Condition Type (ENIGMA)
+
+#### Condition ID Type (ENIGMA)
+Indicates if this variant came from OMIM.  From ENIGMA
+
+#### Condition ID Value (ENIGMA)
+Indicates the disease association for this variant.  From ENIGMA.
+
+#### Source(s)
+List of repositories containing the variant
 
-##### What do these classifications mean?
-- *Pathogenic variants* confer an increased risk of disease. 
-- *Likely pathogenic variants* have good evidence to support an association with disease risk.
-- *Likely benign variants* have good evidence to support no association with disease risk.
-- *Benign variants* are not associated with any markedly increased risk of disease.
-- *Variants of uncertain significance (VUS)* are those for which the evidence of disease risk is not clear yet, sometimes because there is not yet enough evidence to classify them as either pathogenic or benign.
+#### Source URL(s)
+URL(s) pointing back to the original source data
 
-##### My variant is classified pathogenic. What do I do now?
-This website is not intended to provide a clinical diagnosis. Please contact your primary care provider to determine what steps may be necessary.
+#### Submitter (ClinVar)
+Submitting organization.  From ClinVar.
 
-#### Source
+#### URL (ENIGMA)
+URL listing the variant.  From ENIGMA.
 
-The variants shown on this site are stored in larger genomic variant databases.  One major variant datase is [ClinVar](http://www.ncbi.nlm.nih.gov/clinvar/).  This column gives the variant's ID in the ClinVar database, and contains hyperlinks showing the variant in ClinVar.
 
 
 # Variant Detail Page Glossary

content/home.md

@@ -1,3 +1,3 @@
-Search for a specific BRCA1 or BRCA2 variant for more information on that variant. For more information about the BRCA1 and BRCA2 genes, genetic variation, and cancer, please click the *About* link at the top of the page.
+Just type in box above and use auto-complete to search for BRCA1 or BRCA2 variants. For more information about the BRCA1 and BRCA2 genes, genetic variation, and cancer, please click the *About* link at the top of the page.
 
 This website is supported by the BRCA Exchange of the Global Alliance for Genomics and Health. The BRCA Exchange advances our understanding of the genetic basis of breast cancer, ovarian cancer and other diseases by pooling data on BRCA1/2 genetic variants and corresponding clinical data from around the world.