rs201054207
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_002180.3(IGHMBP2):c.808C>T(p.Arg270Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,614,148 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R270H) has been classified as Uncertain significance.
Frequency
Consequence
NM_002180.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGHMBP2 | NM_002180.3 | c.808C>T | p.Arg270Cys | missense_variant | 6/15 | ENST00000255078.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGHMBP2 | ENST00000255078.8 | c.808C>T | p.Arg270Cys | missense_variant | 6/15 | 1 | NM_002180.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152156Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251464Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135912
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 727236
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152276Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74456
ClinVar
Submissions by phenotype
Autosomal recessive distal spinal muscular atrophy 1;C4015349:Charcot-Marie-Tooth disease axonal type 2S Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 30, 2021 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 270 of the IGHMBP2 protein (p.Arg270Cys). This variant is present in population databases (rs201054207, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with IGHMBP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 198144). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt IGHMBP2 protein function. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 09, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at