rs558018
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_016156.6(MTMR2):āc.1634A>Gā(p.Asn545Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,612,936 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.012 ( 35 hom., cov: 32)
Exomes š: 0.0012 ( 40 hom. )
Consequence
MTMR2
NM_016156.6 missense
NM_016156.6 missense
Scores
1
8
9
Clinical Significance
Conservation
PhyloP100: 7.95
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0088483095).
BP6
?
Variant 11-95836284-T-C is Benign according to our data. Variant chr11-95836284-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 194416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-95836284-T-C is described in Lovd as [Benign]. Variant chr11-95836284-T-C is described in Lovd as [Pathogenic].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.012 (1824/152082) while in subpopulation AFR AF= 0.0425 (1763/41518). AF 95% confidence interval is 0.0408. There are 35 homozygotes in gnomad4. There are 866 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 35 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTMR2 | NM_016156.6 | c.1634A>G | p.Asn545Ser | missense_variant | 14/15 | ENST00000346299.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTMR2 | ENST00000346299.10 | c.1634A>G | p.Asn545Ser | missense_variant | 14/15 | 1 | NM_016156.6 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0120 AC: 1820AN: 151964Hom.: 35 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00293 AC: 734AN: 250808Hom.: 12 AF XY: 0.00199 AC XY: 269AN XY: 135516
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GnomAD4 exome AF: 0.00124 AC: 1805AN: 1460854Hom.: 40 Cov.: 32 AF XY: 0.00108 AC XY: 782AN XY: 726724
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GnomAD4 genome ? AF: 0.0120 AC: 1824AN: 152082Hom.: 35 Cov.: 32 AF XY: 0.0116 AC XY: 866AN XY: 74372
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ESP6500AA
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171
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Asia WGS
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 29, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jun 14, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | MTMR2: BS1, BS2 - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 02, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 02, 2015 | - - |
Charcot-Marie-Tooth disease type 4B1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Charcot-Marie-Tooth disease type 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.;.;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;.;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D;D
REVEL
Uncertain
Sift
Benign
D;D;D;D;D
Sift4G
Benign
T;T;T;T;.
Polyphen
B;.;.;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
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