rs61735578

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

demyelinating hereditary motor and sensory neuropathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Charcot-Marie-Tooth disease type 4B1
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

MTMR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 306538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

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

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

GnomAD2 exomes

AF:

0.0348

AC:

8712

AN:

250530

AF XY:

0.0379

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 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

African (AFR)

AF:

0.0571

AC:

1896

AN:

33186

American (AMR)

AF:

0.0111

AC:

495

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.0168

AC:

438

AN:

26038

East Asian (EAS)

AF:

0.000530

AC:

AN:

39604

South Asian (SAS)

AF:

0.0902

AC:

7760

AN:

86016

European-Finnish (FIN)

AF:

0.0758

AC:

4033

AN:

53178

Middle Eastern (MID)

AF:

0.0687

AC:

394

AN:

5734

European-Non Finnish (NFE)

AF:

0.0194

AC:

21422

AN:

1104422

Other (OTH)

AF:

0.0278

AC:

1668

AN:

60080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

1746

3492

5237

6983

8729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

814

1628

2442

3256

4070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0369

AC:

5610

AN:

152096

Hom.:

158

Cov.:

AF XY:

0.0398

AC XY:

2956

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0567

AC:

2354

AN:

41546

American (AMR)

AF:

0.0173

AC:

264

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.0179

AC:

AN:

3468

East Asian (EAS)

AF:

0.000964

AC:

AN:

5188

South Asian (SAS)

AF:

0.0872

AC:

420

AN:

4814

European-Finnish (FIN)

AF:

0.0764

AC:

809

AN:

10594

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0236

AC:

1603

AN:

67934

Other (OTH)

AF:

0.0366

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

256

512

768

1024

1280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0236

Hom.:

Bravo

AF:

0.0312

TwinsUK

AF:

0.0191

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.

Mar 10, 2016

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jun 02, 2017

Athena Diagnostics

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

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

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

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.87

D;.;.;.;D

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.46

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;.;.;.;.

PhyloP100

6.1

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.9

D;D;D;D;D

Sift

Benign

0.092

T;T;T;T;T

Sift4G

Benign

0.11

T;T;T;T;.

Vest4

0.30

ClinPred

0.037

GERP RS

4.6

Varity_R

0.69

gMVP

0.82

Mutation Taster

=87/13

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over