rs3824874

Variant names:

• chr11-95923947-T-A
• rs3824874
• ENST00000352297.11:c.-280A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-95923947-T-A
• chr11-95923947-T-C
• chr11-95923947-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000352297.11(MTMR2):​c.-280A>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 0.00000284 in 1,406,648 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: 33)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: MTMR2 ENST00000352297.11 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000295552 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31934845).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR2	NM_016156.6	c.8A>T	p.Lys3Met	missense_variant	Exon 1 of 15	ENST00000346299.10	NP_057240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTMR2	ENST00000346299.10	c.8A>T	p.Lys3Met	missense_variant	Exon 1 of 15	1	NM_016156.6	ENSP00000345752.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 160886 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000284 AC: 4 AN: 1406648 Hom.: 0 Cov.: 47 AF XY: 0.00000144 AC XY: 1 AN XY: 694654

African (AFR) AF: 0.00 AC: 0 AN: 32072

American (AMR) AF: 0.00 AC: 0 AN: 37048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25224

East Asian (EAS) AF: 0.00 AC: 0 AN: 36276

South Asian (SAS) AF: 0.00 AC: 0 AN: 79998

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49218

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5616

European-Non Finnish (NFE) AF: 0.00000277 AC: 3 AN: 1082914

Other (OTH) AF: 0.0000172 AC: 1 AN: 58282

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.71	T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	1.3	L
PhyloP100		1.5
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.038	D
Polyphen		0.26	B
Vest4		0.29
MutPred		0.15		Loss of ubiquitination at K3 (P = 0.0071);
MVP		0.84
MPC		0.59
ClinPred		0.57	D
GERP RS		0.82
PromoterAI		-0.066	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.48
Mutation Taster		=97/3	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: rs3824874; hg19: chr11-95657111;