11-95845530-G-T

Variant names:

• chr11-95845530-G-T
• rs568878
• NM_016156.6:c.1180-371C>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.1180-371C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,812 control chromosomes in the GnomAD database, including 18,687 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 0.49 (18687 hom., cov: 32)
• Consequence: MTMR2 NM_016156.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR2	NM_016156.6	c.1180-371C>A		intron_variant	Intron 10 of 14	ENST00000346299.10	NP_057240.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTMR2	ENST00000346299.10	c.1180-371C>A		intron_variant	Intron 10 of 14	1	NM_016156.6	ENSP00000345752.6

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74000 AN: 151694 Hom.: 18654 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.657

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.515

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.488 AC: 74076 AN: 151812 Hom.: 18687 Cov.: 32 AF XY: 0.480 AC XY: 35589 AN XY: 74184

African (AFR) AF: 0.598 AC: 24750 AN: 41418

American (AMR) AF: 0.473 AC: 7208 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.657 AC: 2278 AN: 3466

East Asian (EAS) AF: 0.359 AC: 1850 AN: 5150

South Asian (SAS) AF: 0.310 AC: 1493 AN: 4814

European-Finnish (FIN) AF: 0.373 AC: 3920 AN: 10508

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30981 AN: 67898

Other (OTH) AF: 0.520 AC: 1095 AN: 2104

Alfa AF: 0.323 Hom.: 813

Bravo AF: 0.506

Asia WGS AF: 0.360 AC: 1246 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.13
PhyloP100		-0.55
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: rs568878; hg19: chr11-95578694;