11-95836162-G-T

Variant names:

• chr11-95836162-G-T
• rs61735577
• NM_016156.6:c.1756C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.04
• Publications: 5 publications found

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)

ACMG classification

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR2	NM_016156.6	MANE Select	c.1756C>A	p.Arg586Arg	synonymous	Exon 14 of 15	NP_057240.3
	MTMR2	NM_001440647.1		c.1672C>A	p.Arg558Arg	synonymous	Exon 13 of 14	NP_001427576.1
	MTMR2	NM_001440648.1		c.1663C>A	p.Arg555Arg	synonymous	Exon 13 of 14	NP_001427577.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR2	ENST00000346299.10	TSL:1 MANE Select	c.1756C>A	p.Arg586Arg	synonymous	Exon 14 of 15	ENSP00000345752.6	Q13614-1
	MTMR2	ENST00000352297.11	TSL:1	c.1540C>A	p.Arg514Arg	synonymous	Exon 15 of 16	ENSP00000343737.7	Q13614-2
	MTMR2	ENST00000393223.8	TSL:1	c.1540C>A	p.Arg514Arg	synonymous	Exon 15 of 16	ENSP00000376915.3	Q13614-2

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5593 AN: 151772 Hom.: 159 Cov.: 32

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

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.: 32 AF XY: 0.0289 AC XY: 21019 AN XY: 726608

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: 21 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

GnomAD4 genome AF: 0.0368 AC: 5589 AN: 151890 Hom.: 158 Cov.: 32 AF XY: 0.0397 AC XY: 2947 AN XY: 74248

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: 61 AN: 3464

East Asian (EAS) AF: 0.000968 AC: 5 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: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0235 AC: 1597 AN: 67872

Other (OTH) AF: 0.0360 AC: 76 AN: 2112

Alfa AF: 0.0247 Hom.: 46

Bravo AF: 0.0311

Asia WGS AF: 0.0330 AC: 115 AN: 3478

EpiCase AF: 0.0252

EpiControl AF: 0.0247

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Charcot-Marie-Tooth disease (1)
-	-	1	Charcot-Marie-Tooth disease type 4 (1)
-	-	1	Charcot-Marie-Tooth disease type 4B1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.3
DANN	Benign	0.81
PhyloP100		1.0
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61735577; hg19: chr11-95569326; COSMIC: COSV108145943; COSMIC: COSV108145943;