11-95862279-A-T

Position:

• chr11-95862279-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000346299.10(MTMR2):​c.350T>A​(p.Met117Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M117T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MTMR2 ENST00000346299.10 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.84

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR2	NM_016156.6	c.350T>A	p.Met117Lys	missense_variant	4/15	ENST00000346299.10	NP_057240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR2	ENST00000346299.10	c.350T>A	p.Met117Lys	missense_variant	4/15	1	NM_016156.6	ENSP00000345752	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Uncertain	24
DANN	Benign	0.94
DEOGEN2	Uncertain	0.51	D;.;.;.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	0.058
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;.;.;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.48	T;T;T;T;T
MetaSVM	Benign	-0.51	T
MutationAssessor	Benign	0.20	N;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.5	N;N;N;N;N
REVEL	Uncertain	0.38
Sift	Benign	0.34	T;T;T;T;T
Sift4G	Benign	0.49	T;T;T;T;.
Polyphen		0.0	B;.;.;.;.
Vest4		0.81
MutPred		0.49		Gain of ubiquitination at M117 (P = 0.0162);.;.;.;.;
MVP		0.81
MPC		0.51
ClinPred		0.74	D
GERP RS		5.9
Varity_R		0.46
gMVP		0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs752402777; hg19: chr11-95595443;