Variant rs566204 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000346299.10(MTMR2):c.1131C>T(p.Thr377=) 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
ENST00000346299.10 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.242

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 (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 id is 260685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-95847762-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
MTMR2	NM_016156.6 linkuse as main transcript	c.1131C>T	p.Thr377=	synonymous_variant	10/15	ENST00000346299.10	NP_057240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR2	ENST00000346299.10 linkuse as main transcript	c.1131C>T	p.Thr377=	synonymous_variant	10/15	1	NM_016156.6	ENSP00000345752	P3	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

GnomAD3 exomes

AF:

0.298

AC:

74805

AN:

251242

Hom.:

12653

AF XY:

0.300

AC XY:

40719

AN XY:

135786

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 SAS exome

AF:

0.167

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

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.214

Gnomad4 ASJ exome

AF:

0.519

Gnomad4 EAS exome

AF:

0.294

Gnomad4 SAS exome

AF:

0.169

Gnomad4 FIN exome

AF:

0.248

Gnomad4 NFE exome

AF:

0.381

Gnomad4 OTH exome

AF:

0.345

GnomAD4 genome

AF:

0.281

AC:

42724

AN:

151886

Hom.:

7040

Cov.:

AF XY:

0.273

AC XY:

20239

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.269

Gnomad4 ASJ

AF:

0.527

Gnomad4 EAS

AF:

0.264

Gnomad4 SAS

AF:

0.156

Gnomad4 FIN

AF:

0.243

Gnomad4 NFE

AF:

0.379

Gnomad4 OTH

AF:

0.335

Alfa

AF:

0.365

Hom.:

13296

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

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 02, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

Charcot-Marie-Tooth disease type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.6

DANN

Benign

0.52

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

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