17-8161673-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_ModeratePP5_Moderate
The NM_014232.3(VAMP2):c.217G>T(p.Gly73Trp) 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 (★).
Frequency
Consequence
NM_014232.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VAMP2 | ENST00000316509.11 | c.217G>T | p.Gly73Trp | missense_variant | Exon 3 of 5 | 1 | NM_014232.3 | ENSP00000314214.6 | ||
ENSG00000263620 | ENST00000498285.1 | c.217G>T | p.Gly73Trp | missense_variant | Exon 3 of 5 | 4 | ENSP00000464383.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Observed as a de novo variant in internal GeneDx whole exome sequencing data in association with intellectual disability and seizures. In silico analysis supports that this missense variant has a deleterious effect on protein structure/function. Not observed in large population cohorts (Lek et al., 2016).M issense variants in nearby residues reported in the literature in individuals with a neurodevelopmental disorder with autistic features and hypotonia (Salpietro et al., 2019). We interpret G73W as a pathogenic variant. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at