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NM_007294.4(BRCA1):c.964G>C (p.Ala322Pro)

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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: Jan 7, 2021)
Last evaluated:
Oct 29, 2020
Accession:
VCV000055767.11
Variation ID:
55767
Description:
single nucleotide variant
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NM_007294.4(BRCA1):c.964G>C (p.Ala322Pro)

Allele ID
70434
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
17q21.31
Genomic location
17: 43094567 (GRCh38) GRCh38 UCSC
17: 41246584 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000017.11:g.43094567C>G
NC_000017.10:g.41246584C>G
NM_007294.4:c.964G>C MANE Select NP_009225.1:p.Ala322Pro missense
... more HGVS
Protein change
A322P, A275P
Other names
-
Canonical SPDI
NC_000017.11:43094566:C:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Links
ClinGen: CA003989
dbSNP: rs80357252
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 Mar 13, 2019 RCV000483940.4
Likely benign 1 criteria provided, single submitter Oct 29, 2020 RCV000049206.10
Uncertain significance 1 criteria provided, single submitter Aug 24, 2020 RCV000780997.2
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Sep 5, 2018 RCV000218097.4
Conflicting interpretations of pathogenicity 2 no assertion criteria provided May 1, 2012 RCV000083228.4
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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
11983 12150

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Sep 19, 2018)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000566751.5
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted BRCA1 c.964G>C at the cDNA level, p.Ala322Pro (A322P) at the protein level, and results in the change of an Alanine to … (more)
Likely benign
(May 18, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000903583.1
Submitted: (Nov 06, 2018)
Evidence details
Uncertain significance
(Mar 13, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001133659.2
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (3)
Uncertain significance
(Aug 24, 2020)
criteria provided, single submitter
Method: clinical testing
not specified
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000918742.2
Submitted: (Sep 09, 2020)
Evidence details
Publications
PubMed (7)
Comment:
Variant summary: BRCA1 c.964G>C (p.Ala322Pro) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging … (more)
Uncertain significance
(Sep 05, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000277412.5
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (1)
Comment:
The p.A322P variant (also known as c.964G>C), located in coding exon 9 of the BRCA1 gene, results from a G to C substitution at nucleotide … (more)
Likely benign
(Oct 29, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary breast and ovarian cancer syndrome
Allele origin: germline
Invitae
Accession: SCV000077219.10
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
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: SCV000143967.1
Submitted: (Mar 28, 2014)
Evidence details
Benign
(May 01, 2012)
no assertion criteria provided
Method: clinical testing
Breast-ovarian cancer, familial 1
Allele origin: germline
Sharing Clinical Reports Project (SCRP)
Accession: SCV000115302.3
Submitted: (Dec 30, 2013)
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
Prevalence of BRCA1 and BRCA2 Mutations Among High-Risk Saudi Patients With Breast Cancer. Abulkhair O Journal of global oncology 2018 PMID: 30199306
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
Sanger Confirmation Is Required to Achieve Optimal Sensitivity and Specificity in Next-Generation Sequencing Panel Testing. Mu W The Journal of molecular diagnostics : JMD 2016 PMID: 27720647
Patterns and functional implications of rare germline variants across 12 cancer types. Lu C Nature communications 2015 PMID: 26689913
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
Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. Judkins T Cancer research 2005 PMID: 16267036
Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition. Pavlicek A Human molecular genetics 2004 PMID: 15385441
Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation. Abkevich V Journal of medical genetics 2004 PMID: 15235020
The breast cancer information core: database design, structure, and scope. Szabo C Human mutation 2000 PMID: 10923033

Text-mined citations for rs80357252...

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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 Jun 14, 2021