rs267606971
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PP3PP5_Very_Strong
The NM_013382.7(POMT2):c.551C>T(p.Thr184Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000617 in 1,458,108 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 Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. T184T) has been classified as Likely benign.
Frequency
Consequence
NM_013382.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMT2 | NM_013382.7 | c.551C>T | p.Thr184Met | missense_variant | 5/21 | ENST00000261534.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMT2 | ENST00000261534.9 | c.551C>T | p.Thr184Met | missense_variant | 5/21 | 1 | NM_013382.7 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248200Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134142
GnomAD4 exome AF: 0.00000617 AC: 9AN: 1458108Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4AN XY: 725440
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2N Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 30, 2007 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | MGZ Medical Genetics Center | May 04, 2022 | - - |
not provided Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 21, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 15, 2017 | - - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2;C3150416:Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2;C3150418:Autosomal recessive limb-girdle muscular dystrophy type 2N Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2023 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 184 of the POMT2 protein (p.Thr184Met). This variant is present in population databases (rs267606971, gnomAD 0.003%). This missense change has been observed in individuals with muscular dystrophy-dystroglycanopathy (PMID: 17878207, 17923109, 25214167, 27447704, 30060766, 32528171, 33176815, 34413876). ClinVar contains an entry for this variant (Variation ID: 3229). 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 not expected to disrupt POMT2 protein function with a negative predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 25, 2024 | - - |
Intellectual disability Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille | Jan 01, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at