chr14-77298737-G-A
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Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_013382.7(POMT2):c.958C>T(p.Gln320*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,260 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
POMT2
NM_013382.7 stop_gained
NM_013382.7 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 8.04
Genes affected
POMT2 (HGNC:19743): (protein O-mannosyltransferase 2) The protein encoded by this gene is an O-mannosyltransferase that requires interaction with the product of the POMT1 gene for enzymatic function. The encoded protein is found in the membrane of the endoplasmic reticulum. Defects in this gene are a cause of Walker-Warburg syndrome (WWS).[provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-77298737-G-A is Pathogenic according to our data. Variant chr14-77298737-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 289683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-77298737-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
POMT2 | NM_013382.7 | c.958C>T | p.Gln320* | stop_gained | 8/21 | ENST00000261534.9 | NP_037514.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
POMT2 | ENST00000261534.9 | c.958C>T | p.Gln320* | stop_gained | 8/21 | 1 | NM_013382.7 | ENSP00000261534.4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250082Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135088
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461260Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726818
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GnomAD4 genome Cov.: 33
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
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 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 20, 2021 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in POMT2 are known to be pathogenic (PMID: 15894594). This variant has not been reported in the literature in individuals with POMT2-related disease. ClinVar contains an entry for this variant (Variation ID: 289683). This variant is present in population databases (rs775932206, ExAC 0.02%). This sequence change creates a premature translational stop signal (p.Gln320*) in the POMT2 gene. It is expected to result in an absent or disrupted protein product. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 27, 2016 | - - |
Computational scores
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Name
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BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at