rs1555247556
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_002180.3(IGHMBP2):c.1562A>G(p.His521Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,988 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. H521Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_002180.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGHMBP2 | NM_002180.3 | c.1562A>G | p.His521Arg | missense_variant | 11/15 | ENST00000255078.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGHMBP2 | ENST00000255078.8 | c.1562A>G | p.His521Arg | missense_variant | 11/15 | 1 | NM_002180.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1459988Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726078
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Autosomal recessive distal spinal muscular atrophy 1;C4015349:Charcot-Marie-Tooth disease axonal type 2S Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 18, 2019 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with IGHMBP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 466580). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with arginine at codon 521 of the IGHMBP2 protein (p.His521Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at