rs142299878
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_013382.7(POMT2):c.1903G>A(p.Val635Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00098 in 1,613,240 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_013382.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMT2 | NM_013382.7 | c.1903G>A | p.Val635Ile | missense_variant | 19/21 | ENST00000261534.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMT2 | ENST00000261534.9 | c.1903G>A | p.Val635Ile | missense_variant | 19/21 | 1 | NM_013382.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000631 AC: 96AN: 152192Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000492 AC: 123AN: 249938Hom.: 0 AF XY: 0.000532 AC XY: 72AN XY: 135356
GnomAD4 exome AF: 0.00102 AC: 1486AN: 1460930Hom.: 2 Cov.: 34 AF XY: 0.00101 AC XY: 734AN XY: 726800
GnomAD4 genome ? AF: 0.000624 AC: 95AN: 152310Hom.: 0 Cov.: 33 AF XY: 0.000510 AC XY: 38AN XY: 74478
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2019 | Reported in a fetus with lissencephaly without an identified second POMT2 variant (Bouchet et al., 2007); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 17559086, 30564623) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 18, 2018 | - - |
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Mar 31, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 01, 2016 | - - |
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 | Sep 13, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 635 of the POMT2 protein (p.Val635Ile). This variant is present in population databases (rs142299878, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with type II lissencephaly (PMID: 17559086). ClinVar contains an entry for this variant (Variation ID: 194965). 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. 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. - |
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;C4284790:Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at