Submissions for variant NM_004333.6(BRAF):c.2128-26dup

dbSNP: rs370332827

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001192588	SCV001360825	benign	not specified	2019-08-19	criteria provided, single submitter	clinical testing	Variant summary: BRAF c.2128-17dupT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.01 in 16028 control chromosomes in the ExAC database, including 3 homozygotes. The observed variant frequency is approximately 4100 fold of 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 benign. To our knowledge, no occurrence of c.2128-17dupT 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002559214	SCV003250806	benign	RASopathy	2022-01-17	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003973133	SCV004798722	likely benign	BRAF-related disorder	2021-03-02	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).