rs530914

Variant names:

• chr11-95898992-C-T
• rs530914
• NM_016156.6:c.81-10731G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

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.81-10731G>A		intron	N/A	NP_057240.3
	MTMR2	NM_001440647.1		c.81-10731G>A		intron	N/A	NP_001427576.1
	MTMR2	NM_001440648.1		c.81-10731G>A		intron	N/A	NP_001427577.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR2	ENST00000346299.10	TSL:1 MANE Select	c.81-10731G>A		intron	N/A	ENSP00000345752.6	Q13614-1
	MTMR2	ENST00000352297.11	TSL:1	c.-136-10731G>A		intron	N/A	ENSP00000343737.7	Q13614-2
	MTMR2	ENST00000393223.8	TSL:1	c.-136-10731G>A		intron	N/A	ENSP00000376915.3	Q13614-2

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

African (AFR) AF: 0.847 AC: 35167 AN: 41500

American (AMR) AF: 0.523 AC: 7980 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2343 AN: 3470

East Asian (EAS) AF: 0.379 AC: 1964 AN: 5176

South Asian (SAS) AF: 0.448 AC: 2160 AN: 4824

European-Finnish (FIN) AF: 0.488 AC: 5161 AN: 10568

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34437 AN: 67876

Other (OTH) AF: 0.605 AC: 1280 AN: 2114

Alfa AF: 0.535 Hom.: 11613

Bravo AF: 0.615

Asia WGS AF: 0.432 AC: 1502 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.045
DANN	Benign	0.84
PhyloP100		-2.6
Mutation Taster		=100/0	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: rs530914; hg19: chr11-95632156;