ClinVar Miner

Submissions for variant NM_004333.6(BRAF):c.1227A>G (p.Ser409=) (rs145035762)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000033298 SCV000616391 benign Rasopathy 2017-04-03 reviewed by expert panel curation The filtering allele frequency of the c.1227A>G (p.Ser409=) variant in the BRAF gene is 0.313% for European (Non-Finnish) chromosomes by the Exome Aggregation Consortium (233/66620 with 95% CI), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1). Additionally, this variant is a synonymous (silent) variant at a nucleotide that is not highly conserved and is not predicted to impact splicing (BP7). The p.Ser409= variant has been identified in a patient with an alternate molecular basis for disease (BP5; GeneDx, Partners LMM, EGL Genetics internal data; GTR ID's: 21766, 26957, 500060; SCV000057203.8; SCV000061570.5; SCV000112807.7). Computational prediction tools and conservation analysis suggest that the p.Ser409= variant does not impact the protein (BP4). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied: BA1, BP7, BP5, BP4.
GeneDx RCV000680284 SCV000057203 benign not provided 2016-05-31 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000037908 SCV000061570 benign not specified 2012-01-30 criteria provided, single submitter clinical testing Ser409Ser in exon 10 of BRAF: This variant is not expected to have clinical sign ificance because it is not located within the splice consensus sequence, has bee n identified in 0.3% (20/7020) of European American chromosomes and <0.1% (2/373 8) of African American chromosomes by the NHLBI Exome sequencing project in a br oad population (http://evs.gs.washington.edu/EVS; dbSNP rs145035762)
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000037908 SCV000112807 benign not specified 2015-04-07 criteria provided, single submitter clinical testing
Invitae RCV000680284 SCV000252784 benign not provided 2019-02-11 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000037908 SCV000310105 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000349078 SCV000466980 likely benign Noonan syndrome with multiple lentigines 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000384923 SCV000466981 likely benign Cardio-facio-cutaneous syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000290490 SCV000466982 likely benign Noonan syndrome 2016-06-14 criteria provided, single submitter clinical testing

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