ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.305C>G (p.Ala102Gly) (rs80357190)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166160 SCV000216934 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA1) RCV000031086 SCV000144993 uncertain significance Breast-ovarian cancer, familial 1 2004-11-25 no assertion criteria provided clinical testing
Color RCV000166160 SCV000903872 likely benign Hereditary cancer-predisposing syndrome 2016-04-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000048062 SCV000591258 uncertain significance not specified 2015-06-25 criteria provided, single submitter clinical testing
GeneDx RCV000048062 SCV000209905 likely benign not specified 2017-03-31 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000586828 SCV000699001 uncertain significance not provided 2017-07-28 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.305C>G (p.Ala102Gly) variant involves the alteration of a non-conserved nucleotide located in the Zinc finger RING domain. 3/5 in silico tools predict a damaging outcome for this variant. This variant is absent in 120796 control chromosomes. This variant has been reported in at least two HBOC affected individuals with co-occurrence of a BRCA1 deleterious variant, suggesting this variant likely falls in the benign spectrum (Alsop_BRCA1&2_JCO_2012, Palma_BRCA2_Cancer Res_2008). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/VUS, without evidence to independently evaluate. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS)-possibly benign until additional information becomes available.
Invitae RCV000203639 SCV000076075 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-01-01 criteria provided, single submitter clinical testing This sequence change replaces alanine with glycine at codon 102 of the BRCA1 protein (p.Ala102Gly). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and glycine. This variant is not present in population databases (rs80357190, ExAC no frequency). This variant has been reported in a family with hereditary breast and ovarian cancer, as well as an unrelated individual with ovarian cancer (PMID: 18703817, 22711857). This variant was present on the same chromosome with a pathogenic BRCA1 variant in the family (PMID: 18703817). ClinVar contains an entry for this variant (Variation ID: 37505). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000031086 SCV000053682 likely benign Breast-ovarian cancer, familial 1 2012-07-17 no assertion criteria provided clinical testing

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