rs397516894
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_001374258.1(BRAF):c.1840C>T(p.His614Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H614Q) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001374258.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAF | NM_001374258.1 | c.1840C>T | p.His614Tyr | missense_variant | 15/20 | ENST00000644969.2 | |
BRAF | NM_004333.6 | c.1720C>T | p.His574Tyr | missense_variant | 14/18 | ENST00000646891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAF | ENST00000644969.2 | c.1840C>T | p.His614Tyr | missense_variant | 15/20 | NM_001374258.1 | |||
BRAF | ENST00000646891.2 | c.1720C>T | p.His574Tyr | missense_variant | 14/18 | NM_004333.6 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Cardio-facio-cutaneous syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 02, 2013 | The His574Tyr variant in BRAF has not been reported in the literature nor previo usly identified by our laboratory. This variant was not identified in either par ent of this individual and therefore likely occurred de novo, assuming that non- medical explanations including alternate paternity or undisclosed adoption have been ruled out. In addition, this variant has not been identified in large popul ations by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). Computational analyses (biochemical amino acid properties, conservation, AlignG VGD, PolyPhen2, and SIFT) suggest that the variant may impact the protein, thoug h this information is not predictive enough to determine pathogenicity. Given th e de novo occurrence of this variant in a proband with clinical features of Card io-facio-cutaneous syndrome, this variant is highly likely to be pathogenic. In summary, this variant meets our criteria to be classified as pathogenic (http:// pcpgm.partners.org/LMM). - |
not provided Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - CFC International | - | Variant interpreted as Uncertain significance and reported on 08-17-2012 by Lab or GTR ID 21766. GenomeConnect-CFC International assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at