rs546809

Variant names:

• chr11-95846774-A-G
• rs546809
• NM_016156.6:c.1179+940T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016156.6(MTMR2):​c.1179+940T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,116 control chromosomes in the GnomAD database, including 7,151 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 0.28 (7151 hom., cov: 32)
• Consequence: MTMR2 NM_016156.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTMR2	NM_016156.6	c.1179+940T>C		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.1179+940T>C		intron_variant	Intron 10 of 14	1	NM_016156.6	ENSP00000345752.6

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42754 AN: 151998 Hom.: 7145 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.281 AC: 42763 AN: 152116 Hom.: 7151 Cov.: 32 AF XY: 0.273 AC XY: 20270 AN XY: 74356

African (AFR) AF: 0.123 AC: 5124 AN: 41516

American (AMR) AF: 0.270 AC: 4116 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1828 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1377 AN: 5170

South Asian (SAS) AF: 0.157 AC: 756 AN: 4822

European-Finnish (FIN) AF: 0.245 AC: 2596 AN: 10592

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.380 AC: 25850 AN: 67956

Other (OTH) AF: 0.336 AC: 710 AN: 2116

Alfa AF: 0.317 Hom.: 1115

Bravo AF: 0.280

Asia WGS AF: 0.225 AC: 780 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.47
PhyloP100		0.29
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: rs546809; hg19: chr11-95579938;