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NM_007294.4(BRCA1):c.2060A>C (p.Gln687Pro)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(2);Uncertain significance(4)

Review status:
criteria provided, conflicting interpretations
Submissions:
8 (Most recent: Sep 24, 2021)
Last evaluated:
Mar 19, 2021
Accession:
VCV000037443.11
Variation ID:
37443
Description:
single nucleotide variant
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NM_007294.4(BRCA1):c.2060A>C (p.Gln687Pro)

Allele ID
45999
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q21.31
Genomic location
17: 43093471 (GRCh38) GRCh38 UCSC
17: 41245488 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
U14680.1:n.2179A>C
NC_000017.10:g.41245488T>G
NC_000017.11:g.43093471T>G
... more HGVS
Protein change
Q687P, Q640P
Other names
2179A>C
Canonical SPDI
NC_000017.11:43093470:T:G
Functional consequence
-
Global minor allele frequency (GMAF)
0.00020 (G)

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00006
Trans-Omics for Precision Medicine (TOPMed) 0.00002
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD), exomes 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
Links
ClinGen: CA001364
dbSNP: rs28897680
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Feb 1, 2019 RCV000129968.8
Uncertain significance 2 criteria provided, multiple submitters, no conflicts Mar 19, 2021 RCV000587889.3
Likely benign 1 criteria provided, single submitter Nov 12, 2020 RCV000047696.10
Likely benign 1 criteria provided, single submitter Jan 20, 2020 RCV001659764.1
Conflicting interpretations of pathogenicity 2 no assertion criteria provided Mar 15, 2010 RCV000031024.5
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
BRCA1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
12287 12455

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(May 15, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000698913.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (5)
Comment:
Variant summary: The BRCA1 c.2060A>C (p.Gln687Pro) variant involves the alteration of a non-conserved nucleotide and is not located in some of the known domains in … (more)
Uncertain significance
(Feb 01, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000683009.3
Submitted: (May 19, 2020)
Evidence details
Likely benign
(Nov 12, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Invitae
Accession: SCV000075709.10
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Uncertain significance
(Nov 14, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000184792.6
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (3)
Comment:
The p.Q687P variant (also known as c.2060A>C), located in coding exon 9 of the BRCA1 gene, results from an A to C substitution at nucleotide … (more)
Likely benign
(Jan 20, 2020)
criteria provided, single submitter
Method: curation
Breast-ovarian cancer, familial 1
Breast-ovarian cancer, familial 2
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Research and Development, ARUP Laboratories
Accession: SCV001878220.1
Submitted: (Sep 09, 2021)
Evidence details
Publications
PubMed (1)
Other databases
https://arup.utah.edu/database/B…
Uncertain significance
(Mar 19, 2021)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000565959.5
Submitted: (Sep 24, 2021)
Evidence details
Comment:
Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on … (more)
Uncertain significance
(May 29, 2002)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000144283.1
Submitted: (Mar 28, 2014)
Evidence details
Likely benign
(Mar 15, 2010)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Sharing Clinical Reports Project (SCRP)
Accession: SCV000053617.3
Submitted: (Jun 20, 2012)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification. Parsons MT Human mutation 2019 PMID: 31131967
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
A reliable method for the detection of BRCA1 and BRCA2 mutations in fixed tumour tissue utilising multiplex PCR-based targeted next generation sequencing. Ellison G BMC clinical pathology 2015 PMID: 25859162
Missense variants of uncertain significance (VUS) altering the phosphorylation patterns of BRCA1 and BRCA2. Tram E PloS one 2013 PMID: 23704879
Interlaboratory diagnostic validation of conformation-sensitive capillary electrophoresis for mutation scanning. Mattocks CJ Clinical chemistry 2010 PMID: 20167696
Identification and in silico analysis of functional SNPs of the BRCA1 gene. Rajasekaran R Genomics 2007 PMID: 17719744
Natural selection and mammalian BRCA1 sequences: elucidating functionally important sites relevant to breast cancer susceptibility in humans. Burk-Herrick A Mammalian genome : official journal of the International Mammalian Genome Society 2006 PMID: 16518693
Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition. Pavlicek A Human molecular genetics 2004 PMID: 15385441
The breast cancer information core: database design, structure, and scope. Szabo C Human mutation 2000 PMID: 10923033
https://arup.utah.edu/database/BRCA/Variants/BRCA1.php - - - -

Text-mined citations for rs28897680...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 26, 2021