11-95923880-C-T

Variant names:

• chr11-95923880-C-T
• rs1376231939
• NM_016156.6:c.75G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_016156.6(MTMR2):​c.75G>A​(p.Leu25Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,402,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MTMR2 NM_016156.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.210
• 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)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 11-95923880-C-T is Benign according to our data. Variant chr11-95923880-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 543440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.21 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016156.6. 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.75G>A	p.Leu25Leu	synonymous	Exon 1 of 15	NP_057240.3
	MTMR2	NM_001440647.1		c.75G>A	p.Leu25Leu	synonymous	Exon 1 of 14	NP_001427576.1
	MTMR2	NM_001440648.1		c.75G>A	p.Leu25Leu	synonymous	Exon 1 of 14	NP_001427577.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTMR2	ENST00000346299.10	TSL:1 MANE Select	c.75G>A	p.Leu25Leu	synonymous	Exon 1 of 15	ENSP00000345752.6	Q13614-1
	MTMR2	ENST00000352297.11	TSL:1	c.-213G>A		5_prime_UTR	Exon 1 of 16	ENSP00000343737.7	Q13614-2
	MTMR2	ENST00000393223.8	TSL:1	c.-234G>A		5_prime_UTR	Exon 1 of 16	ENSP00000376915.3	Q13614-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000653 AC: 1 AN: 153084 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: 0.0000173

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1402070 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 691994

African (AFR) AF: 0.00 AC: 0 AN: 31818

American (AMR) AF: 0.00 AC: 0 AN: 36196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25186

East Asian (EAS) AF: 0.00 AC: 0 AN: 36008

South Asian (SAS) AF: 0.00 AC: 0 AN: 79528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1080940

Other (OTH) AF: 0.00 AC: 0 AN: 58132

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Charcot-Marie-Tooth disease type 4 (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.88
PhyloP100		0.21
PromoterAI		0.092	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1376231939; hg19: chr11-95657044;