chr11-95858149-G-A

Position:

• chr11-95858149-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016156.6(MTMR2):​c.570+382C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0617 in 152,158 control chromosomes in the GnomAD database, including 373 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.062 (373 hom., cov: 32)
• Consequence: MTMR2 NM_016156.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR2	NM_016156.6	c.570+382C>T		intron_variant		ENST00000346299.10	NP_057240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR2	ENST00000346299.10	c.570+382C>T		intron_variant		1	NM_016156.6	ENSP00000345752	P3

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 9367 AN: 152042 Hom.: 372 Cov.: 32

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.0557

Gnomad EAS AF: 0.0499

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0390

Gnomad OTH AF: 0.0640

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0617 AC: 9383 AN: 152158 Hom.: 373 Cov.: 32 AF XY: 0.0652 AC XY: 4850 AN XY: 74388

Gnomad4 AFR AF: 0.0949

Gnomad4 AMR AF: 0.0521

Gnomad4 ASJ AF: 0.0557

Gnomad4 EAS AF: 0.0500

Gnomad4 SAS AF: 0.0429

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0391

Gnomad4 OTH AF: 0.0633

Alfa AF: 0.0434 Hom.: 248

Bravo AF: 0.0595

Asia WGS AF: 0.0450 AC: 157 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.5
DANN	Benign	0.63

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: rs10501831; hg19: chr11-95591313;