11-95923941-G-A

Variant names:

• chr11-95923941-G-A
• rs778430688
• ENST00000352297.11:c.-274C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_201278.3(MTMR2):​c.-397C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,408,284 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MTMR2 NM_201278.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05
• Publications: 0 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: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000295552 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19764215).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201278.3. 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.14C>T	p.Ser5Leu	missense	Exon 1 of 15	NP_057240.3
	MTMR2	NM_001243571.2		c.-470C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 18	NP_001230500.1	Q13614-2
	MTMR2	NM_001440631.1		c.-554C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 19	NP_001427560.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR2	ENST00000352297.11	TSL:1	c.-274C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000343737.7	Q13614-2
	MTMR2	ENST00000393223.8	TSL:1	c.-295C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 16	ENSP00000376915.3	Q13614-2
	MTMR2	ENST00000346299.10	TSL:1 MANE Select	c.14C>T	p.Ser5Leu	missense	Exon 1 of 15	ENSP00000345752.6	Q13614-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1408284 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 695578

African (AFR) AF: 0.00 AC: 0 AN: 32144

American (AMR) AF: 0.00 AC: 0 AN: 37222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25240

East Asian (EAS) AF: 0.00 AC: 0 AN: 36376

South Asian (SAS) AF: 0.00 AC: 0 AN: 80084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.00000277 AC: 3 AN: 1083954

Other (OTH) AF: 0.00 AC: 0 AN: 58348

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	0.69	N
PhyloP100		3.1
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.1	N
REVEL	Uncertain	0.29
Sift	Benign	0.047	D
Sift4G	Benign	0.21	T
Polyphen		0.0	B
Vest4		0.26
MutPred		0.16		Loss of phosphorylation at S5 (P = 0.005)
MVP		0.88
MPC		0.29
ClinPred		0.72	D
GERP RS		4.5
PromoterAI		0.0022	Neutral
Varity_R		0.21
gMVP		0.43
Mutation Taster		=290/10	polymorphism

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: rs778430688; hg19: chr11-95657105;