Submissions for variant NM_004333.6(BRAF):c.2196C>G (p.Ser732=)

gnomAD frequency: 0.00005  dbSNP: rs142592480

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000825118	SCV000966373	likely benign	not specified	2018-04-30	criteria provided, single submitter	clinical testing	p.Ser732Ser in Exon 18 of BRAF: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence. It has been identified in 9/11716 European chro mosomes by the Genome Aggregation Database (gnomAD, http://gnomad.gs.washington. edu/EVS; dbSNP rs142592480). ACMG/AMP Criteria applied: BP4, BP7.
Illumina Laboratory Services, Illumina	RCV001159453	SCV001321170	uncertain significance	Noonan syndrome 7	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001164394	SCV001326518	uncertain significance	LEOPARD syndrome 3	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV001468343	SCV001672385	likely benign	RASopathy	2021-11-26	criteria provided, single submitter	clinical testing
GeneDx	RCV000475603	SCV001792923	likely benign	not provided	2019-04-02	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000475603	SCV002563977	likely benign	not provided	2022-07-01	criteria provided, single submitter	clinical testing	BRAF: BP4, BP7
Ambry Genetics	RCV002431383	SCV002728585	likely benign	Cardiovascular phenotype	2019-06-21	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003932773	SCV004763497	likely benign	BRAF-related condition	2020-09-30	criteria provided, single submitter	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).