ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.755G>A (p.Arg252His) (rs80357138)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000049120 SCV000077133 likely benign Hereditary breast and ovarian cancer syndrome 2017-10-16 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129300 SCV000184061 likely benign Hereditary cancer-predisposing syndrome 2017-07-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype,In silico models in agreement (benign),Other strong data supporting benign classification
GeneDx RCV000283401 SCV000329118 uncertain significance not provided 2017-08-04 criteria provided, single submitter clinical testing This variant is denoted BRCA1 c.755G>A at the cDNA level, p.Arg252His (R252H) at the protein level, and results in the change of an Arginine to a Histidine (CGT>CAT). This variant, previously published as BRCA1 874G>A using alternate nomenclature, has been reported in at least one family with breast and/or ovarian cancer (Anczuk?w 2008). BRCA1 Arg252His was not observed in large population cohorts (Lek 2016, The 1000 Genomes Consortium 2015, NHLBI Exome Sequencing Project). Since Arginine and Histidine share similar properties, this is considered a conservative amino acid substitution. BRCA1 Arg252His occurs at a position that is not conserved and is located in the p53 domain 1 and a region known to interact with multiple other proteins (Zhang 1998, Chai 1999, Paul 2014). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether BRCA1 Arg252His is pathogenic or benign. We consider it to be a variant of uncertain significance.
Counsyl RCV000112781 SCV000488926 uncertain significance Breast-ovarian cancer, familial 1 2016-07-19 criteria provided, single submitter clinical testing
Mendelics RCV000049120 SCV000839295 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Color RCV000129300 SCV000903584 likely benign Hereditary cancer-predisposing syndrome 2017-02-21 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112781 SCV000145676 uncertain significance Breast-ovarian cancer, familial 1 2002-05-29 no assertion criteria provided clinical testing

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