ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.708C>T (p.Asn236=) (rs138333692)

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Total submissions: 6
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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)
Illumina Clinical Services Laboratory,Illumina RCV000370230 SCV000466992 likely benign Cardio-facio-cutaneous syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000278004 SCV000466993 likely benign Noonan syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000330619 SCV000466994 likely benign Noonan syndrome with multiple lentigines 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America 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.
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).

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