rs687559

chr11-95865465-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016156.6(MTMR2):c.262+136T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 834,660 control chromosomes in the GnomAD database, including 120,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (29265 hom., cov: 31)
  • Exomes 𝑓: 0.51 (91705 hom.)
• Consequence: MTMR2 NM_016156.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.48

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 11-95865465-A-G is Benign according to our data. Variant chr11-95865465-A-G is described in ClinVar as [Benign]. Clinvar id is 683213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTMR2	NM_016156.6	c.262+136T>C		intron_variant		ENST00000346299.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTMR2	ENST00000346299.10	c.262+136T>C		intron_variant		1	NM_016156.6	P3

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90890 AN: 151906 Hom.: 29207 Cov.: 31

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.601

GnomAD4 exome AF: 0.513 AC: 349875 AN: 682634 Hom.: 91705 Cov.: 9 AF XY: 0.509 AC XY: 186688 AN XY: 366740

Gnomad4 AFR exome AF: 0.851

Gnomad4 AMR exome AF: 0.491

Gnomad4 ASJ exome AF: 0.682

Gnomad4 EAS exome AF: 0.434

Gnomad4 SAS exome AF: 0.460

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.507

Gnomad4 OTH exome AF: 0.544

GnomAD4 genome AF: 0.599 AC: 91006 AN: 152026 Hom.: 29265 Cov.: 31 AF XY: 0.593 AC XY: 44031 AN XY: 74308

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.606

Alfa AF: 0.545 Hom.: 4727

Bravo AF: 0.615

Asia WGS AF: 0.438 AC: 1523 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	7.0
Dann	Benign	0.42

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

Other links and lift over

dbSNP: rs687559; hg19: chr11-95598629; COSMIC: COSV60578875; COSMIC: COSV60578875;