ClinVar Miner

Submissions for variant NM_001374258.1(BRAF):c.708C>T (p.Asn236=) (rs138333692)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000521784 SCV000616462 benign Rasopathy 2017-04-18 reviewed by expert panel curation The filtering allele frequency of the c.708C>T (p.Asn236=) variant in the BRAF gene is 0.116% (27/16412) of South Asian 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)
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037951 SCV000061616 likely benign not specified 2008-11-24 criteria provided, single submitter clinical testing Asn236Asn in exon 5 of BRAF: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue, is not located near a s plice junction, and has been identified in <1% of chromosomes from a broad but c linically and racially unspecified population (dbSNP rs138333692).
Illumina Clinical Services Laboratory,Illumina RCV000278004 SCV000466993 uncertain significance 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, 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 RCV000330619 SCV000466994 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 RCV000037951 SCV000916700 benign not specified 2018-04-02 criteria provided, single submitter clinical testing Variant summary: BRAF c.708C>T alters a conserved nucleotide resulting in a synonymous change. 4/5 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 0.00026 in 276344 control chromosomes in the gnomAD database, including 1 homozygotes. The observed variant frequency is approximately 105.67 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.708C>T in individuals affected with Noonan Syndrome and Related Conditions and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000521784 SCV001002410 benign Rasopathy 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV001705679 SCV001859543 benign not provided 2018-12-10 criteria provided, single submitter clinical testing

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