rs398124264
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_013382.7(POMT2):c.320C>T(p.Pro107Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,878 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 (★★). Synonymous variant affecting the same amino acid position (i.e. P107P) has been classified as Likely benign.
Frequency
Consequence
NM_013382.7 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 |
---|---|---|---|---|---|---|---|
POMT2 | NM_013382.7 | c.320C>T | p.Pro107Leu | missense_variant | 2/21 | ENST00000261534.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMT2 | ENST00000261534.9 | c.320C>T | p.Pro107Leu | missense_variant | 2/21 | 1 | NM_013382.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152102Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251236Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135806
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461776Hom.: 0 Cov.: 30 AF XY: 0.0000316 AC XY: 23AN XY: 727170
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152102Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74276
ClinVar
Submissions by phenotype
not provided Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 25, 2023 | Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools predict that this variant is damaging. The variant is located in a region that is considered important for protein function and/or structure. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 06, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 22, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 03, 2018 | Previously identified in a patient who harbored a second POMT2 variant through exome sequencing, however, detailed clinical information about the patient was not provided (Meng et al., 2017); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 28973083) - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | 3billion | May 22, 2022 | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.93; 3Cnet: 0.92). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with POMT2 related disorder (PMID: 28973083). However, the evidence of pathogenicity is insufficient at this time and it is classified as auncertain significancein ClinVar (ClinVar ID: VCV000095543) Therefore, this variant is classified as uncertain significanceaccording to the recommendation of ACMG/AMP guideline. - |
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 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 107 of the POMT2 protein (p.Pro107Leu). This variant is present in population databases (rs398124264, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of POMT2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 95543). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. - |
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