Submissions for variant NM_004333.6(BRAF):c.36G>A (p.Ala12=)

gnomAD frequency: 0.00011  dbSNP: rs397507454

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000033265	SCV000616466	benign	RASopathy	2017-04-18	reviewed by expert panel	curation	The filtering allele frequency of the c.36G>A (p.Ala12=) variant in the BRAF gene is 0.116% (14/7290) 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)
GeneDx	RCV000590400	SCV000057170	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000380281	SCV000467001	likely benign	Noonan syndrome 7	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000283347	SCV000467002	likely benign	LEOPARD syndrome 3	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590400	SCV000698339	benign	not provided	2017-07-31	criteria provided, single submitter	clinical testing	Variant summary: The BRAF c.36G>A (p.Ala12Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 3/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 83/134502 control chromosomes in genomAD at a frequency of 0.0006171, which is approximately 247 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/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Invitae	RCV000033265	SCV000776930	benign	RASopathy	2023-12-08	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000590400	SCV001746009	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	BRAF: BP4, BP7
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813215	SCV002060470	likely benign	Noonan syndrome and Noonan-related syndrome	2016-12-12	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002345261	SCV002621311	likely benign	Cardiovascular phenotype	2022-05-14	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	RCV003944862	SCV004757705	likely benign	BRAF-related condition	2020-08-17	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).