ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.976A>G (p.Ile326Val) (rs775040765)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000462938 SCV000616461 benign Rasopathy 2017-04-18 reviewed by expert panel curation The filtering allele frequency of the c.1772A>G (p.Asn591Ser) variant in the SOS1 gene is 0.054% (11/11524) of Latino chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581)
Invitae RCV000462938 SCV000563670 likely benign Rasopathy 2019-12-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589220 SCV000698350 benign not provided 2017-03-12 criteria provided, single submitter clinical testing Variant summary: The c.976A>G (p.Ile326Val) in BRAF gene is a missense change that involves a non-conserved nucleotide and 5/5 in silico tools predict benign outcome. The variant is located outside of any known functional domain and behaved like wildtype in phosphorylation assay (Razzaque_2007). The variant is present in the large control population datasets of ExAC and gnomAD at a frequency 0.00009 and 0.000075, respectively (11/ 121408 and 21/ 277182 chrs tested, respectively), predominantly in individuals of East Asian descent ( allele frequency: 0.00104 and 0.0007, respectively). These frequencies exceed the maximal estimated expected frequency of a pathogenic allele (0.0000025) in this gene. The variant was identified in one patient with Noonan syndrome who also carried a de novo mutation in BRAF gene, p. E501K, a known pathogenic variant associated with CFC. Taking together, the variant was classified as Benign.

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