ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3010A>G (p.Ser1004Gly)

dbSNP: rs398122759
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000232614 SCV000283202 likely benign Hereditary breast ovarian cancer syndrome 2023-01-22 criteria provided, single submitter clinical testing
Counsyl RCV000077702 SCV000489468 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2016-10-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV000565814 SCV000668553 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-27 criteria provided, single submitter clinical testing The p.S1004G variant (also known as c.3010A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 3010. The serine at codon 1004 is replaced by glycine, an amino acid with similar properties. This alteration was identified in a cohort of unselected breast cancer patients in China (Li G et al. J. Cancer Res. Clin. Oncol. 2017 Oct;143:2011-2024). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000565814 SCV001353894 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-30 criteria provided, single submitter clinical testing This missense variant replaces serine with glycine at codon 1004 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast cancer (PMID: 28664449, 33471991; Leiden Open Variation Database DB-ID BRCA2_007146, 35731312). This variant has been identified in 1/250722 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001811354 SCV001473283 uncertain significance not provided 2020-01-21 criteria provided, single submitter clinical testing The BRCA2 c.3010A>G; p.Ser1004Gly variant (rs398122759), is reported in the literature in at least one individual with breast cancer (Li 2017). This variant is reported in ClinVar (Variation ID: 91794), and is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The serine at codon 1004 is weakly conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Ser1004Gly variant is uncertain at this time. References: Li G et al. Analysis of BRCA1/2 mutation spectrum and prevalence in unselected Chinese breast cancer patients by next-generation sequencing. J Cancer Res Clin Oncol. 2017 Oct;143(10):2011-2024.
University of Washington Department of Laboratory Medicine, University of Washington RCV000565814 SCV003850313 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
All of Us Research Program, National Institutes of Health RCV000077702 SCV004845097 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-12-07 criteria provided, single submitter clinical testing This missense variant replaces serine with glycine at codon 1004 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast cancer (PMID: 28664449, 33471991; Leiden Open Variation Database DB-ID BRCA2_007146, 35731312). This variant has been identified in 1/250722 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000077702 SCV000109505 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2012-05-03 no assertion criteria provided clinical testing

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