ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1068A>G (p.Gln356=) (rs143335467)

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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 RCV000524069 SCV000616460 benign Rasopathy 2017-04-18 reviewed by expert panel curation The filtering allele frequency of the c.1068A>G (p.Gln356=) variant in the BRAF gene is 0.115% (27/16512) 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 RCV000037898 SCV000061560 likely benign not specified 2008-11-04 criteria provided, single submitter clinical testing Gln356Gln in exon 8 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 rs143335467).
Illumina Clinical Services Laboratory,Illumina RCV000345522 SCV000466983 likely benign Noonan syndrome with multiple lentigines 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000406467 SCV000466984 likely benign Cardio-facio-cutaneous syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000305967 SCV000466985 likely benign Noonan syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000037898 SCV000916699 benign not specified 2018-04-02 criteria provided, single submitter clinical testing Variant summary: BRAF c.1068A>G alters a non-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 277200 control chromosomes in the gnomAD database, including 1 homozygotes. The observed variant frequency is approximately 105.34 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.1068A>G 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 RCV000861983 SCV001002409 benign not provided 2018-10-25 criteria provided, single submitter clinical testing

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