rs1471799706
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002180.3(IGHMBP2):c.2912G>A(p.Arg971Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,613,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IGHMBP2 | NM_002180.3 | c.2912G>A | p.Arg971Lys | missense_variant | Exon 15 of 15 | ENST00000255078.8 | NP_002171.2 | |
IGHMBP2 | XM_017017670.3 | c.1901G>A | p.Arg634Lys | missense_variant | Exon 11 of 11 | XP_016873159.1 | ||
IGHMBP2 | XM_005273975.4 | c.1784G>A | p.Arg595Lys | missense_variant | Exon 8 of 8 | XP_005274032.1 | ||
IGHMBP2 | XM_011544994.2 | c.1679G>A | p.Arg560Lys | missense_variant | Exon 8 of 8 | XP_011543296.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000806 AC: 2AN: 248206Hom.: 0 AF XY: 0.0000149 AC XY: 2AN XY: 134570
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460982Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726800
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74378
ClinVar
Submissions by phenotype
Autosomal recessive distal spinal muscular atrophy 1;C4015349:Charcot-Marie-Tooth disease axonal type 2S Uncertain:1
This sequence change replaces arginine with lysine at codon 971 of the IGHMBP2 protein (p.Arg971Lys). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with IGHMBP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 534917). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at