ClinVar Miner

Submissions for variant NM_001374258.1(BRAF):c.1068A>G (p.Gln356=) (rs143335467)

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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 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 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.
Illumina Clinical Services Laboratory,Illumina RCV000305967 SCV000466985 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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 RCV000524069 SCV001002409 benign Rasopathy 2019-12-31 criteria provided, single submitter clinical testing

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