chr7-140777032-A-G
Variant summary
Our verdict is Pathogenic. Variant got 19 ACMG points: 19P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_001374258.1(BRAF):c.1694T>C(p.Leu565Pro) 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. L565Q) 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 19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAF | NM_001374258.1 | c.1694T>C | p.Leu565Pro | missense_variant | 14/20 | ENST00000644969.2 | |
BRAF | NM_004333.6 | c.1574T>C | p.Leu525Pro | missense_variant | 13/18 | ENST00000646891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAF | ENST00000644969.2 | c.1694T>C | p.Leu565Pro | missense_variant | 14/20 | NM_001374258.1 | |||
BRAF | ENST00000646891.2 | c.1574T>C | p.Leu525Pro | missense_variant | 13/18 | NM_004333.6 | P4 | ||
ENST00000700122.1 | n.502+2164A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes | Apr 05, 2018 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Molecular Diagnostics Lab, Nemours Children's Health, Delaware | Jul 22, 2015 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Sep 21, 2020 | The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 17551924, 33482860, 24803665, 23093928, 19206169, 26150740, 24458522) - |
Noonan syndrome 7 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Oct 25, 2021 | This variant was identified as de novo (maternity and paternity confirmed)._x000D_ Criteria applied: PS2, PM5_STR, PS4_MOD, PM1, PM2_SUP, PP3 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at