rs753188177
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_016156.6(MTMR2):c.507G>A(p.Gly169Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,476 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 (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
MTMR2
NM_016156.6 synonymous
NM_016156.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.00600
Publications
0 publications found
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]
MTMR2 Gene-Disease associations (from GenCC):
- demyelinating hereditary motor and sensory neuropathyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- Charcot-Marie-Tooth disease type 4B1Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
Variant 11-95858594-C-T is Benign according to our data. Variant chr11-95858594-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 476876.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.006 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_016156.6. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MTMR2 | NM_016156.6 | MANE Select | c.507G>A | p.Gly169Gly | synonymous | Exon 6 of 15 | NP_057240.3 | ||
| MTMR2 | NM_001440647.1 | c.507G>A | p.Gly169Gly | synonymous | Exon 6 of 14 | NP_001427576.1 | |||
| MTMR2 | NM_001440648.1 | c.507G>A | p.Gly169Gly | synonymous | Exon 6 of 14 | NP_001427577.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MTMR2 | ENST00000346299.10 | TSL:1 MANE Select | c.507G>A | p.Gly169Gly | synonymous | Exon 6 of 15 | ENSP00000345752.6 | ||
| MTMR2 | ENST00000352297.11 | TSL:1 | c.291G>A | p.Gly97Gly | synonymous | Exon 7 of 16 | ENSP00000343737.7 | ||
| MTMR2 | ENST00000393223.8 | TSL:1 | c.291G>A | p.Gly97Gly | synonymous | Exon 7 of 16 | ENSP00000376915.3 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000796 AC: 2AN: 251134 AF XY: 0.00000737 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
251134
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460476Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 726632 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1460476
Hom.:
Cov.:
29
AF XY:
AC XY:
1
AN XY:
726632
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33434
American (AMR)
AF:
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26114
East Asian (EAS)
AF:
AC:
0
AN:
39600
South Asian (SAS)
AF:
AC:
1
AN:
86228
European-Finnish (FIN)
AF:
AC:
0
AN:
53312
Middle Eastern (MID)
AF:
AC:
0
AN:
5756
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1110974
Other (OTH)
AF:
AC:
0
AN:
60338
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
ClinVar submissions as Germline
Significance:Likely benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
1
Charcot-Marie-Tooth disease type 4 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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