Submissions for variant NM_004333.6(BRAF):c.1929A>G (p.Gly643=)

gnomAD frequency: 0.30796  dbSNP: rs9648696

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000033338	SCV000616456	benign	RASopathy	2017-04-18	reviewed by expert panel	curation	The filtering allele frequency of the c.1929A>G (p.Gly643=) variant in the BRAF gene is 66.117% (6984/10356) of African 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)
GeneDx	RCV000033338	SCV000057243	benign	RASopathy	2012-01-24	criteria provided, single submitter	clinical testing	The variant is found in NOONAN panel(s).
Eurofins Ntd Llc (ga)	RCV000037940	SCV000058308	benign	not specified	2015-05-19	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037940	SCV000061605	benign	not specified	2007-12-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000037940	SCV000310111	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000306807	SCV000466968	benign	Noonan syndrome 7	2018-01-13	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000361471	SCV000466969	benign	LEOPARD syndrome 3	2018-01-13	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000037940	SCV000918664	benign	not specified	2017-11-16	criteria provided, single submitter	clinical testing	Variant summary: The BRAF c.1929A>G (p.Gly643Gly) variant involves the alteration of a nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant does not affect any ESE site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 25661/120836 control chromosomes at a frequency of 0.2123622, which is approximately 84945 times the estimated maximal expected allele frequency of a pathogenic BRAF variant (0.0000025), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000033338	SCV001000055	benign	RASopathy	2024-02-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000509253	SCV001158928	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002408490	SCV002720704	benign	Cardiovascular phenotype	2018-12-04	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Breakthrough Genomics, Breakthrough Genomics	RCV000509253	SCV005270690	benign	not provided		criteria provided, single submitter	not provided
Baylor Genetics	RCV000033338	SCV000196685	benign	RASopathy		no assertion criteria provided	clinical testing	Variant classified using ACMG guidelines
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000037940	SCV000207628	benign	not specified	2015-01-15	no assertion criteria provided	clinical testing
GenomeConnect, ClinGen	RCV000509253	SCV000607337	not provided	not provided		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.