rs530914

chr11-95898992-C-T

Variant summary

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

The NM_016156.6(MTMR2):c.81-10731G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,984 control chromosomes in the GnomAD database, including 29,283 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 0.60 (29283 hom., cov: 32)
• Consequence: MTMR2 NM_016156.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTMR2	NM_016156.6	c.81-10731G>A		intron_variant		ENST00000346299.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTMR2	ENST00000346299.10	c.81-10731G>A		intron_variant		1	NM_016156.6	P3

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90922 AN: 151866 Hom.: 29227 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.601

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

GnomAD4 genome AF: 0.599 AC: 91036 AN: 151984 Hom.: 29283 Cov.: 32 AF XY: 0.593 AC XY: 44039 AN XY: 74306

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.675

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.605

Alfa AF: 0.532 Hom.: 10216

Bravo AF: 0.615

Asia WGS AF: 0.432 AC: 1502 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.045
Dann	Benign	0.84

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: rs530914; hg19: chr11-95632156;