rs142155860
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_016156.6(MTMR2):c.547G>T(p.Ala183Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00216 in 1,611,186 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0046 ( 17 hom., cov: 32)
Exomes 𝑓: 0.0019 ( 56 hom. )
Consequence
MTMR2
NM_016156.6 missense
NM_016156.6 missense
Scores
2
10
6
Clinical Significance
Conservation
PhyloP100: 7.16
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 Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.009640455).
BP6
Variant 11-95858554-C-A is Benign according to our data. Variant chr11-95858554-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 306544.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00456 (695/152262) while in subpopulation NFE AF= 0.000926 (63/68002). AF 95% confidence interval is 0.000742. There are 17 homozygotes in gnomad4. There are 530 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 17 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MTMR2 | NM_016156.6 | c.547G>T | p.Ala183Ser | missense_variant | 6/15 | ENST00000346299.10 | NP_057240.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MTMR2 | ENST00000346299.10 | c.547G>T | p.Ala183Ser | missense_variant | 6/15 | 1 | NM_016156.6 | ENSP00000345752 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00457 AC: 695AN: 152144Hom.: 17 Cov.: 32
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GnomAD3 exomes AF: 0.00474 AC: 1190AN: 251052Hom.: 27 AF XY: 0.00455 AC XY: 617AN XY: 135696
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GnomAD4 exome AF: 0.00191 AC: 2791AN: 1458924Hom.: 56 Cov.: 29 AF XY: 0.00184 AC XY: 1333AN XY: 725978
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GnomAD4 genome AF: 0.00456 AC: 695AN: 152262Hom.: 17 Cov.: 32 AF XY: 0.00712 AC XY: 530AN XY: 74454
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease type 4B1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Charcot-Marie-Tooth disease type 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 22, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;.;.;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Uncertain
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;.
Polyphen
P;.;.;.;.
Vest4
MVP
MPC
ClinPred
T
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Varity_R
gMVP
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