rs752626893

Positions:

• chr11-95838198-C-A
• chr11-95838198-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000346299.10(MTMR2):​c.1489G>T​(p.Ala497Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. A497T) 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: 7.83

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.804

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTMR2	NM_016156.6	c.1489G>T	p.Ala497Ser	missense_variant	13/15	ENST00000346299.10	NP_057240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTMR2	ENST00000346299.10	c.1489G>T	p.Ala497Ser	missense_variant	13/15	1	NM_016156.6	ENSP00000345752	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.82	D;.;.;.;D
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.86	D;D;.;.;D
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.80	D;D;D;D;D
MetaSVM	Uncertain	0.44	D
MutationAssessor	Benign	1.3	L;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-2.9	D;D;D;D;D
REVEL	Pathogenic	0.70
Sift	Benign	0.054	T;T;T;T;T
Sift4G	Benign	0.15	T;T;T;T;.
Polyphen		0.85	P;.;.;.;.
Vest4		0.68
MutPred		0.62		Loss of helix (P = 0.1706);.;.;.;.;
MVP		0.88
MPC		0.34
ClinPred		0.97	D
GERP RS		4.6
Varity_R		0.67
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-95571362;