ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.68T>A (p.Met23Lys)

dbSNP: rs746778122
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000702844 SCV000831715 likely benign RASopathy 2022-12-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779849 SCV000916702 benign not specified 2018-09-02 criteria provided, single submitter clinical testing Variant summary: BRAF c.68T>A (p.Met23Lys) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function (Mutation Taster not included due to low p-value). The variant allele was found at a frequency of 8.3e-05 in 121194 control chromosomes, predominantly at a frequency of 0.00045 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 180-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in BRAF causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.68T>A in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences RCV004752999 SCV005367243 uncertain significance BRAF-related disorder 2024-08-28 no assertion criteria provided clinical testing The BRAF c.68T>A variant is predicted to result in the amino acid substitution p.Met23Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.045% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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