rs566204

Variant names:

• chr11-95847762-G-A
• rs566204
• NM_016156.6:c.1131C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 0.242
• Publications: 32 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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.

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.1131C>T	p.Thr377Thr	synonymous	Exon 10 of 15	NP_057240.3
	MTMR2	NM_001440647.1		c.1047C>T	p.Thr349Thr	synonymous	Exon 9 of 14	NP_001427576.1
	MTMR2	NM_001440648.1		c.1131C>T	p.Thr377Thr	synonymous	Exon 10 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.1131C>T	p.Thr377Thr	synonymous	Exon 10 of 15	ENSP00000345752.6	Q13614-1
	MTMR2	ENST00000352297.11	TSL:1	c.915C>T	p.Thr305Thr	synonymous	Exon 11 of 16	ENSP00000343737.7	Q13614-2
	MTMR2	ENST00000393223.8	TSL:1	c.915C>T	p.Thr305Thr	synonymous	Exon 11 of 16	ENSP00000376915.3	Q13614-2

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42715 AN: 151768 Hom.: 7036 Cov.: 32

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

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.: 38 AF XY: 0.346 AC XY: 251280 AN XY: 726080

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

GnomAD4 genome AF: 0.281 AC: 42724 AN: 151886 Hom.: 7040 Cov.: 32 AF XY: 0.273 AC XY: 20239 AN XY: 74260

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: 85 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25743 AN: 67884

Other (OTH) AF: 0.335 AC: 707 AN: 2108

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.6
DANN	Benign	0.52
PhyloP100		0.24
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs566204; hg19: chr11-95580926; COSMIC: COSV60578565; COSMIC: COSV60578565;