NM_016156.6:c.1504G>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016156.6(MTMR2):c.1504G>C(p.Glu502Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0273 in 1,605,020 control chromosomes in the GnomAD database, including 1,053 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 158 hom., cov: 32)

Exomes 𝑓: 0.026 ( 895 hom. )

Consequence

MTMR2
NM_016156.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:8

Conservation

PhyloP100: 6.09

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0067712367).

BP6

Variant 11-95838183-C-G is Benign according to our data. Variant chr11-95838183-C-G is described in ClinVar as [Benign]. Clinvar id is 306538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-95838183-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR2	NM_016156.6 link	c.1504G>C	p.Glu502Gln	missense_variant	Exon 13 of 15	ENST00000346299.10	NP_057240.3	Q13614-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTMR2	ENST00000346299.10 link	c.1504G>C	p.Glu502Gln	missense_variant	Exon 13 of 15	1	NM_016156.6	ENSP00000345752.6		Q13614-1

Frequencies

GnomAD3 genomes

AF:

0.0369

AC:

5613

AN:

151980

Hom.:

159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0568

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0173

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0876

Gnomad FIN

AF:

0.0764

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0236

Gnomad OTH

AF:

0.0375

GnomAD3 exomes

AF:

0.0348

AC:

8712

AN:

250530

Hom.:

285

AF XY:

0.0379

AC XY:

5132

AN XY:

135374

show subpopulations

Gnomad AFR exome

AF:

0.0541

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.000761

Gnomad SAS exome

AF:

0.0903

Gnomad FIN exome

AF:

0.0801

Gnomad NFE exome

AF:

0.0231

Gnomad OTH exome

AF:

0.0337

GnomAD4 exome

AF:

0.0262

AC:

38127

AN:

1452924

Hom.:

895

Cov.:

AF XY:

0.0285

AC XY:

20649

AN XY:

723270

show subpopulations

Gnomad4 AFR exome

AF:

0.0571

Gnomad4 AMR exome

AF:

0.0111

Gnomad4 ASJ exome

AF:

0.0168

Gnomad4 EAS exome

AF:

0.000530

Gnomad4 SAS exome

AF:

0.0902

Gnomad4 FIN exome

AF:

0.0758

Gnomad4 NFE exome

AF:

0.0194

Gnomad4 OTH exome

AF:

0.0278

GnomAD4 genome

AF:

0.0369

AC:

5610

AN:

152096

Hom.:

158

Cov.:

AF XY:

0.0398

AC XY:

2956

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0567

Gnomad4 AMR

AF:

0.0173

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.0872

Gnomad4 FIN

AF:

0.0764

Gnomad4 NFE

AF:

0.0236

Gnomad4 OTH

AF:

0.0366

Alfa

AF:

0.0236

Hom.:

Bravo

AF:

0.0312

TwinsUK

AF:

0.0191

AC:

ALSPAC

AF:

0.0215

AC:

ESP6500AA

AF:

0.0561

AC:

247

ESP6500EA

AF:

0.0212

AC:

182

ExAC

AF:

0.0360

AC:

4375

Asia WGS

AF:

0.0350

AC:

121

AN:

3478

EpiCase

AF:

0.0254

EpiControl

AF:

0.0250

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease type 4B1

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jun 02, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 10, 2016

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Uncertain:1Benign:1

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Inherited Neuropathy Consortium

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease

Benign:1

Molecular Genetics Laboratory, London Health Sciences Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Charcot-Marie-Tooth disease type 4

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.87

D;.;.;.;D

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

D;D;.;.;D

MetaRNN

Benign

0.0068

T;T;T;T;T

MetaSVM

Uncertain

-0.041

MutationAssessor

Uncertain

2.9

M;.;.;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.9

D;D;D;D;D

REVEL

Pathogenic

0.69

Sift

Benign

0.092

T;T;T;T;T

Sift4G

Benign

0.11

T;T;T;T;.

Polyphen

0.66

P;.;.;.;.

Vest4

0.30

MPC

0.43

ClinPred

0.037

GERP RS

4.6

Varity_R

0.69

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over