chr3-87240754-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_014043.4(CHMP2B):āc.90A>Cā(p.Arg30Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R30G) has been classified as Likely benign.
Frequency
Consequence
NM_014043.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHMP2B | NM_014043.4 | c.90A>C | p.Arg30Ser | missense_variant | 2/6 | ENST00000263780.9 | |
CHMP2B | NM_001410777.1 | c.186A>C | p.Arg62Ser | missense_variant | 3/7 | ||
CHMP2B | XM_011533576.3 | c.138A>C | p.Arg46Ser | missense_variant | 2/6 | ||
CHMP2B | NM_001244644.2 | c.4-4960A>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHMP2B | ENST00000263780.9 | c.90A>C | p.Arg30Ser | missense_variant | 2/6 | 1 | NM_014043.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251290Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135814
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461366Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3AN XY: 727018
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Frontotemporal dementia and/or amyotrophic lateral sclerosis 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 11, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with CHMP2B-related conditions. This variant is present in population databases (rs775142652, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 30 of the CHMP2B protein (p.Arg30Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at