ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.497A>T (p.His166Leu) (rs876658364)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219636 SCV000273479 uncertain significance Hereditary cancer-predisposing syndrome 2015-10-01 criteria provided, single submitter clinical testing The p.H166L variant (also known as c.497A>T), located in coding exon 5 of the BRCA2 gene, results from an A to T substitution at nucleotide position 497. The histidine at codon 166 is replaced by leucine, an amino acid withsimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6502 samples (13004 alleles) with coverage of 6502 at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 150000 alleles tested) in our clinical cohort. This amino acid position is poorlyconserved 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 p.H166Lremains unclear.
Invitae RCV000560532 SCV000635418 likely benign Hereditary breast and ovarian cancer syndrome 2020-09-24 criteria provided, single submitter clinical testing
Color Health, Inc RCV000219636 SCV000904824 likely benign Hereditary cancer-predisposing syndrome 2018-02-01 criteria provided, single submitter clinical testing
GeneDx RCV001561823 SCV001784491 uncertain significance not provided 2019-05-15 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Sharing Clinical Reports Project (SCRP) RCV000238704 SCV000297532 benign Breast-ovarian cancer, familial 2 2011-03-07 no assertion criteria provided clinical testing

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