rs1358449243
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_016156.6(MTMR2):βc.464_465delβ(p.Cys155Ter) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000312 in 1,604,134 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β ). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: π 0.0000066 ( 0 hom., cov: 32)
Exomes π: 0.0000028 ( 0 hom. )
Consequence
MTMR2
NM_016156.6 frameshift
NM_016156.6 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.31
Genes affected
MTMR2 (HGNC:7450): (myotubularin related protein 2) This gene is a member of the myotubularin family of phosphoinositide lipid phosphatases. The encoded protein possesses phosphatase activity towards phosphatidylinositol-3-phosphate and phosphatidylinositol-3,5-bisphosphate. Mutations in this gene are a cause of Charcot-Marie-Tooth disease type 4B, an autosomal recessive demyelinating neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
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Very rare variant in population databases, with high coverage;
PP5
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Variant 11-95861994-TAC-T is Pathogenic according to our data. Variant chr11-95861994-TAC-T is described in ClinVar as [Pathogenic]. Clinvar id is 543342.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTMR2 | NM_016156.6 | c.464_465del | p.Cys155Ter | frameshift_variant | 5/15 | ENST00000346299.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTMR2 | ENST00000346299.10 | c.464_465del | p.Cys155Ter | frameshift_variant | 5/15 | 1 | NM_016156.6 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250402Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135440
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GnomAD4 exome AF: 0.00000276 AC: 4AN: 1451898Hom.: 0 AF XY: 0.00000415 AC XY: 3AN XY: 723038
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74376
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease type 4 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 23, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MTMR2 are known to be pathogenic (PMID: 10802647). This variant has not been reported in the literature in individuals with MTMR2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Cys155*) in the MTMR2 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
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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