ClinVar Miner

Submissions for variant NM_007300.4(BRCA1):c.4828C>T (p.Arg1610Cys) (rs80357002)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000048655 SCV000076668 likely benign Hereditary breast and ovarian cancer syndrome 2017-06-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000166139 SCV000216911 likely benign Hereditary cancer-predisposing syndrome 2015-06-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification
GeneDx RCV000437561 SCV000516130 likely benign not specified 2016-05-19 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.
Color RCV000166139 SCV000683212 likely benign Hereditary cancer-predisposing syndrome 2016-11-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587292 SCV000699173 uncertain significance not provided 2016-08-28 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.4765C>T (p.Arg1589Cys) variant causes a missense change involving a non-conserved nucleotide with 2/4 in silico tools (SNPs&GO not captured due to low reliability index) predict a benign outcome. This variant is not located in any known domain/repeats, however lies in flanking region of BRCA2 repeat regions (InterPro). The variant of interest was observed in the large and broad control population from ExAC with an allele frequency of 2/121346 (1/60673), which does not exceed the estimated maximal expected allele frequency for a pathogenic BRCA1 variant of 1/1000. The variant has been reported in HBOC families, however with limited information (i.e. no data about co-occurrence and cosegregation provided). However, a reputable database (BIC) cites the variant to co-occur with a pathogenic BRCA2 variant (c.1929delG), suggesting that it was not a primary cause of disease in the patient. In addition, this variant had similar transcription activation activity in comparison to wildtype (Woods_2016). Multiple reputable databases/clinical laboratories cite the variant as "uncertain significance" (n=2) or "likely benign/benign" (n=2). Another variant at the same residue (p.Arg1589His) has also been reported in UMD five times, one of which also carried a deleterious variant in BRCA2 (c.317-2A>G) and results in transcription activation similar to wildtype (Woods_2016). Therefore, taken all available information into consideration, the variant of interest has been classified as a variant of uncertain significance (VUS)-possibly benign/possible normal variant until additional information becomes available.
Sharing Clinical Reports Project (SCRP) RCV000083212 SCV000115286 benign Breast-ovarian cancer, familial 1 2012-08-10 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083212 SCV000145176 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
True Health Diagnostics RCV000166139 SCV000805232 likely benign Hereditary cancer-predisposing syndrome 2018-05-30 no assertion criteria provided clinical testing

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