rs566204

Variant names:

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.1131C>T(p.Thr377Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 1,611,344 control chromosomes in the GnomAD database, including 100,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7040 hom., cov: 32)

Exomes 𝑓: 0.35 ( 93676 hom. )

Consequence

MTMR2
NM_016156.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.242

Publications

32 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 (BayesDel_noAF=-0.7).

BP6

Variant 11-95847762-G-A is Benign according to our data. Variant chr11-95847762-G-A is described in ClinVar as Benign. ClinVar VariationId is 260685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR2	NM_016156.6 link	c.1131C>T	p.Thr377Thr	synonymous_variant	Exon 10 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.1131C>T	p.Thr377Thr	synonymous_variant	Exon 10 of 15	1	NM_016156.6	ENSP00000345752.6		Q13614-1

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42715

AN:

151768

Hom.:

7036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.352

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.527

Gnomad EAS

AF:

0.263

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.379

Gnomad OTH

AF:

0.329

GnomAD2 exomes

AF:

0.298

AC:

74805

AN:

251242

AF XY:

0.300

show subpopulations

Gnomad AFR exome

AF:

0.125

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.520

Gnomad EAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.246

Gnomad NFE exome

AF:

0.379

Gnomad OTH exome

AF:

0.347

GnomAD4 exome

AF:

0.351

AC:

511845

AN:

1459458

Hom.:

93676

Cov.:

AF XY:

0.346

AC XY:

251280

AN XY:

726080

show subpopulations

African (AFR)

AF:

0.121

AC:

4046

AN:

33444

American (AMR)

AF:

0.214

AC:

9559

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

13542

AN:

26116

East Asian (EAS)

AF:

0.294

AC:

11654

AN:

39652

South Asian (SAS)

AF:

0.169

AC:

14597

AN:

86230

European-Finnish (FIN)

AF:

0.248

AC:

13223

AN:

53332

Middle Eastern (MID)

AF:

0.303

AC:

1747

AN:

5762

European-Non Finnish (NFE)

AF:

0.381

AC:

422640

AN:

1109882

Other (OTH)

AF:

0.345

AC:

20837

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

17310

34620

51931

69241

86551

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12978

25956

38934

51912

64890

<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:

0.281

AC:

42724

AN:

151886

Hom.:

7040

Cov.:

AF XY:

0.273

AC XY:

20239

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.127

AC:

5261

AN:

41458

American (AMR)

AF:

0.269

AC:

4105

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.527

AC:

1829

AN:

3470

East Asian (EAS)

AF:

0.264

AC:

1364

AN:

5162

South Asian (SAS)

AF:

0.156

AC:

750

AN:

4812

European-Finnish (FIN)

AF:

0.243

AC:

2559

AN:

10546

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.379

AC:

25743

AN:

67884

Other (OTH)

AF:

0.335

AC:

707

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1455

2911

4366

5822

7277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.354

Hom.:

15754

Bravo

AF:

0.280

Asia WGS

AF:

0.223

AC:

773

AN:

3478

EpiCase

AF:

0.389

EpiControl

AF:

0.386

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease type 4B1

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 02, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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 04, 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

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.6

(source)

DANN

Benign

0.52

PhyloP100

0.24

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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