chr11-95836162-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016156.6(MTMR2):c.1756C>A(p.Arg586Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 1,612,476 control chromosomes in the GnomAD database, including 1,070 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: 0.027 ( 912 hom. )

Consequence

MTMR2
NM_016156.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.04

Publications

5 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 11-95836162-G-T is Benign according to our data. Variant chr11-95836162-G-T is described in ClinVar as Benign. ClinVar VariationId is 306536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR2	NM_016156.6 link	c.1756C>A	p.Arg586Arg	synonymous_variant	Exon 14 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.1756C>A	p.Arg586Arg	synonymous_variant	Exon 14 of 15	1	NM_016156.6	ENSP00000345752.6

Frequencies

GnomAD3 genomes

AF:

0.0369

AC:

5593

AN:

151772

Hom.:

159

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0567

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0173

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.0869

Gnomad FIN

AF:

0.0770

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0235

Gnomad OTH

AF:

0.0368

GnomAD2 exomes

AF:

0.0347

AC:

8709

AN:

251076

AF XY:

0.0378

show subpopulations

Gnomad AFR exome

AF:

0.0540

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.000761

Gnomad FIN exome

AF:

0.0798

Gnomad NFE exome

AF:

0.0230

Gnomad OTH exome

AF:

0.0338

GnomAD4 exome

AF:

0.0267

AC:

38934

AN:

1460586

Hom.:

912

Cov.:

AF XY:

0.0289

AC XY:

21019

AN XY:

726608

show subpopulations

African (AFR)

AF:

0.0573

AC:

1915

AN:

33422

American (AMR)

AF:

0.0111

AC:

496

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0170

AC:

444

AN:

26084

East Asian (EAS)

AF:

0.000529

AC:

AN:

39682

South Asian (SAS)

AF:

0.0907

AC:

7823

AN:

86236

European-Finnish (FIN)

AF:

0.0767

AC:

4097

AN:

53388

Middle Eastern (MID)

AF:

0.0675

AC:

389

AN:

5760

European-Non Finnish (NFE)

AF:

0.0199

AC:

22066

AN:

1110984

Other (OTH)

AF:

0.0279

AC:

1683

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

2034

4068

6102

8136

10170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

848

1696

2544

3392

4240

<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:

0.0368

AC:

5589

AN:

151890

Hom.:

158

Cov.:

AF XY:

0.0397

AC XY:

2947

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.0565

AC:

2343

AN:

41452

American (AMR)

AF:

0.0173

AC:

263

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3464

East Asian (EAS)

AF:

0.000968

AC:

AN:

5164

South Asian (SAS)

AF:

0.0866

AC:

416

AN:

4806

European-Finnish (FIN)

AF:

0.0770

AC:

814

AN:

10574

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0235

AC:

1597

AN:

67872

Other (OTH)

AF:

0.0360

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

265

530

794

1059

1324

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:

0.0247

Hom.:

Bravo

AF:

0.0311

Asia WGS

AF:

0.0330

AC:

115

AN:

3478

EpiCase

AF:

0.0252

EpiControl

AF:

0.0247

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease type 4B1

Benign:2

Jun 02, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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 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

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.3

(source)

DANN

Benign

0.81

PhyloP100

1.0

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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