rs767737380
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_016156.6(MTMR2):āc.1303T>Cā(p.Leu435=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,613,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00011 ( 0 hom., cov: 32)
Exomes š: 0.000012 ( 0 hom. )
Consequence
MTMR2
NM_016156.6 synonymous
NM_016156.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.228
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
Variant 11-95845036-A-G is Benign according to our data. Variant chr11-95845036-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 543512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.228 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTMR2 | NM_016156.6 | c.1303T>C | p.Leu435= | synonymous_variant | 11/15 | ENST00000346299.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTMR2 | ENST00000346299.10 | c.1303T>C | p.Leu435= | synonymous_variant | 11/15 | 1 | NM_016156.6 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152184Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250960Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135610
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461690Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727142
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74350
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Charcot-Marie-Tooth disease type 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 31, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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