rs200072932
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002180.3(IGHMBP2):c.2456C>T(p.Pro819Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,604,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P819P) has been classified as Likely benign.
Frequency
Consequence
NM_002180.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IGHMBP2 | NM_002180.3 | c.2456C>T | p.Pro819Leu | missense_variant | 13/15 | ENST00000255078.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IGHMBP2 | ENST00000255078.8 | c.2456C>T | p.Pro819Leu | missense_variant | 13/15 | 1 | NM_002180.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000133 AC: 3AN: 226094Hom.: 0 AF XY: 0.0000243 AC XY: 3AN XY: 123380
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1451742Hom.: 0 Cov.: 35 AF XY: 0.00000277 AC XY: 2AN XY: 721422
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152350Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74514
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 | Jun 15, 2018 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine 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. This variant has not been reported in the literature in individuals with IGHMBP2-related disease. This variant is present in population databases (rs200072932, ExAC 0.03%). This sequence change replaces proline with leucine at codon 819 of the IGHMBP2 protein (p.Pro819Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at