ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1959A>G (p.Lys653=) (rs767530204)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000494940 SCV000578312 likely benign Breast-ovarian cancer, familial 1 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Ambry Genetics RCV000166049 SCV000216810 likely benign Hereditary cancer-predisposing syndrome 2014-09-19 criteria provided, single submitter clinical testing
Invitae RCV000466500 SCV000560273 likely benign Hereditary breast and ovarian cancer syndrome 2017-05-23 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590627 SCV000698900 likely benign not provided 2016-07-15 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.1959A>G (p.Lys653Lys) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1/121332 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). In addition, one clinical diagnostic laboratory and a reputable database classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. One LCA sample also carried a pathogenic variant in RAD51C c.93delG/p.Phe32SerfsX8. Taken together, this variant is classified as likely benign, until more evidence becomes available.
Color RCV000166049 SCV000912044 likely benign Hereditary cancer-predisposing syndrome 2018-04-10 criteria provided, single submitter clinical testing
GeneDx RCV000590627 SCV000984051 likely benign not provided 2018-04-12 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.

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