NM_016156.6:c.1504G>C

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.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:9

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: Orphanet, Ambry Genetics, 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.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MTMR2	NM_016156.6	MANE Select	c.1504G>C	p.Glu502Gln	missense	Exon 13 of 15	NP_057240.3
MTMR2	NM_001440647.1		c.1420G>C	p.Glu474Gln	missense	Exon 12 of 14	NP_001427576.1
MTMR2	NM_001440648.1		c.1411G>C	p.Glu471Gln	missense	Exon 12 of 14	NP_001427577.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTMR2	ENST00000346299.10	TSL:1 MANE Select	c.1504G>C	p.Glu502Gln	missense	Exon 13 of 15	ENSP00000345752.6	Q13614-1
MTMR2	ENST00000352297.11	TSL:1	c.1288G>C	p.Glu430Gln	missense	Exon 14 of 16	ENSP00000343737.7	Q13614-2
MTMR2	ENST00000393223.8	TSL:1	c.1288G>C	p.Glu430Gln	missense	Exon 14 of 16	ENSP00000376915.3	Q13614-2

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:

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Charcot-Marie-Tooth disease type 4B1 (2)

not provided (2)

Charcot-Marie-Tooth disease (1)

Charcot-Marie-Tooth disease type 4 (1)

Computational scores

Source: dbNSFP v4.9

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

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.97

MetaRNN

Benign

0.0068

MetaSVM

Uncertain

-0.041

MutationAssessor

Uncertain

2.9

PhyloP100

6.1

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.9

REVEL

Pathogenic

0.69

Sift

Benign

0.092

Sift4G

Benign

0.11

Polyphen

0.66

Vest4

0.30

MPC

0.43

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over