rs869025340
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_001374258.1(BRAF):c.1694T>G(p.Leu565Arg) 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 Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L565P) 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.1694T>G | p.Leu565Arg | missense_variant | 14/20 | ENST00000644969.2 | |
BRAF | NM_004333.6 | c.1574T>G | p.Leu525Arg | missense_variant | 13/18 | ENST00000646891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAF | ENST00000644969.2 | c.1694T>G | p.Leu565Arg | missense_variant | 14/20 | NM_001374258.1 | |||
BRAF | ENST00000646891.2 | c.1574T>G | p.Leu525Arg | missense_variant | 13/18 | NM_004333.6 | P4 | ||
ENST00000700122.1 | n.502+2164A>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Malignant lymphoma, large B-cell, diffuse Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Department Of Pathology & Laboratory Medicine, University Of Pennsylvania | Dec 04, 2023 | Post-initial therapy specimen. - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | May 22, 2015 | The L525R missense change has not been published as a pathogenic variant nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L525R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is highly conserved across species. A different amino acid substitution at the same position (L525P) and missense variants in nearby residues (W531C, G534R) have been reported in the Human Gene Mutation Database in association with disorders in the Noonan syndrome spectrum (Stenson et al., 2009), supporting the functional importance of this region of the protein. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at