14-77320440-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_013382.7(POMT2):āc.242A>Cā(p.His81Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,394,252 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H81R) has been classified as Uncertain significance.
Frequency
Consequence
NM_013382.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMT2 | NM_013382.7 | c.242A>C | p.His81Pro | missense_variant | 1/21 | ENST00000261534.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMT2 | ENST00000261534.9 | c.242A>C | p.His81Pro | missense_variant | 1/21 | 1 | NM_013382.7 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000682 AC: 1AN: 146650Hom.: 0 AF XY: 0.0000127 AC XY: 1AN XY: 78440
GnomAD4 exome AF: 0.00000143 AC: 2AN: 1394252Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1AN XY: 687982
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
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 13, 2021 | This sequence change replaces histidine with proline at codon 81 of the POMT2 protein (p.His81Pro). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and proline. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of POMT2-related conditions (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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