ClinVar Miner

Submissions for variant NM_001374258.1(BRAF):c.1452G>A (p.Arg484=) (rs56101602)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000033300 SCV000616458 benign Rasopathy 2017-04-18 reviewed by expert panel curation The filtering allele frequency of the c.1332G>A (p.Arg444=) variant in the BRAF gene is 0.077% (64/66708) of European 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 RCV000033300 SCV000057205 poly Rasopathy criteria provided, single submitter clinical testing Converted during submission to Benign.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000037911 SCV000058305 benign not specified 2013-03-18 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000037911 SCV000061573 benign not specified 2012-10-16 criteria provided, single submitter clinical testing Arg444Arg in exon 11 of BRAF: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and it has been identified in 0.16% (14/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs56101602)
Invitae RCV000033300 SCV000252785 benign Rasopathy 2020-12-08 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000333893 SCV000466977 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 Clinical Services Laboratory,Illumina RCV000388426 SCV000466978 benign 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 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 RCV000588198 SCV000698332 benign not provided 2017-02-06 criteria provided, single submitter clinical testing Variant summary: The BRAF c.1332G>A variant involves the alteration of non-conserved nucleotide, resulting in synonymous amino acid change. It is predicted to have no significant effect on splicing by 4/5 splice prediction tools. The variant is found in ExAC with an allele frequency of 0.00058 (71/121302 chromosomes), predominantly in European (Non-Finnish) subpopulation with an allele frequency of 0.00095 (64/66708 chromosomes). This frequency is about 384 times the estimated maximal allele frequency of a pathogenic variant in BRAF gene (2.5e10-6), strongly supporting that this is likely a benign variant found mainly in European (Non-Finnish) subpopulation. Multiple clinical laboratories/reputable databases have classified this variant as benign/likely benign. Taken together, this variant is classified as Benign.

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