ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.64G>A (p.Asp22Asn) (rs397507456)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000520051 SCV000616392 benign Rasopathy 2017-04-03 reviewed by expert panel curation The variant c.64G>A (p.Asp22Asn) in BRAF was observed in a healthy adult individual who did not have clinical features of a RASopathy (BS2; Partners LMM and GeneDx internal data; GTR ID's: 21766, 26957; SCV000061615.5, SCV000057172.10). This variant has been observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder (BP2_Strong; LabCorp internal data GTR ID: 500026, ClinVar SCV000698345.1). In summary, this variant meets criteria to be classified as benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BP2_S, BS2.
GeneDx RCV000590699 SCV000057172 benign not provided 2016-05-31 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.
ITMI RCV000037950 SCV000084406 not provided not specified 2013-09-19 no assertion provided reference population
Integrated Genetics/Laboratory Corporation of America RCV000590699 SCV000698345 benign not provided 2017-07-17 criteria provided, single submitter clinical testing Variant summary: The BRAF c.64G>A (p.Asp22Asn) variant involves the alteration of a conserved nucleotide and 2/4 in silico tools (SNPsandGO not captured due to low reliability index)predict a benign outcome. However, these predictions have yet to be functionally assessed. This variant was found in 106/151790 control chromosomes, predominantly observed in East Asian subpopulation at a frequency of 0.009248 (102/11030). This frequency is about 3699 times the estimated maximal expected allele frequency of a pathogenic BRAF variant (0.0000025), suggesting this is likely a benign polymorphism found primarily in population(s) of East Asian origin. Multiple publications have cited the variant in individuals affected with various cancers indicated predominantly being a somatic occurrence, although limited information as to whether the variant was eliminated from being a germline occurrence was indicated. An internal LCA sample carrying this variant also carried another pathogenic variant PTPN11 p.Thr42Ala. Multiple clinical diagnostic laboratories have conflicting classifications "benign" or "uncertain significance." However, due the high occurrence in controls and the co-occurrence with a pathogenic PTPN11 variant, the variant of interest has been classified as Benign.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000037950 SCV000061615 uncertain significance not specified 2015-02-19 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory

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