rs11552794

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003863.4(DPM2):c.183G>A(p.Leu61Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00978 in 1,583,806 control chromosomes in the GnomAD database, including 1,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 117 hom., cov: 33)

Exomes 𝑓: 0.0095 ( 896 hom. )

Consequence

DPM2
NM_003863.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.23

Publications

6 publications found

Variant links:

Genes affected

DPM2 (HGNC:3006): (dolichyl-phosphate mannosyltransferase subunit 2, regulatory) Dolichol-phosphate mannose (Dol-P-Man) serves as a donor of mannosyl residues on the lumenal side of the endoplasmic reticulum (ER). Lack of Dol-P-Man results in defective surface expression of GPI-anchored proteins. Dol-P-Man is synthesized from GDP-mannose and dolichol-phosphate on the cytosolic side of the ER by the enzyme dolichyl-phosphate mannosyltransferase. The protein encoded by this gene is a hydrophobic protein that contains 2 predicted transmembrane domains and a putative ER localization signal near the C terminus. This protein associates with DPM1 in vivo and is required for the ER localization and stable expression of DPM1 and also enhances the binding of dolichol-phosphate to DPM1. [provided by RefSeq, Jul 2008]

DPM2 Gene-Disease associations (from GenCC):

congenital muscular dystrophy with intellectual disability and severe epilepsy
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia, Orphanet

DPM2 links:

ENSG00000227218 (HGNC:):

ENSG00000227218 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 9-127936566-C-T is Benign according to our data. Variant chr9-127936566-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 128919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.23 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPM2	NM_003863.4 link	c.183G>A	p.Leu61Leu	synonymous_variant	Exon 3 of 4	ENST00000314392.13	NP_003854.1	O94777
DPM2	NM_001378437.1 link	c.93G>A	p.Leu31Leu	synonymous_variant	Exon 2 of 3		NP_001365366.1
DPM2	NR_165631.1 link	n.340G>A		non_coding_transcript_exon_variant	Exon 3 of 4
DPM2	NR_165632.1 link	n.38-786G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPM2	ENST00000314392.13 link	c.183G>A	p.Leu61Leu	synonymous_variant	Exon 3 of 4	1	NM_003863.4	ENSP00000322181.8		O94777

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1960

AN:

152178

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0235

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.0322

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.0289

AC:

6716

AN:

232578

AF XY:

0.0257

show subpopulations

Gnomad AFR exome

AF:

0.000704

Gnomad AMR exome

AF:

0.0608

Gnomad ASJ exome

AF:

0.00291

Gnomad EAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.0323

Gnomad NFE exome

AF:

0.00171

Gnomad OTH exome

AF:

0.0170

GnomAD4 exome

AF:

0.00945

AC:

13531

AN:

1431510

Hom.:

896

Cov.:

AF XY:

0.00922

AC XY:

6536

AN XY:

708634

show subpopulations

African (AFR)

AF:

0.000617

AC:

AN:

32420

American (AMR)

AF:

0.0534

AC:

2209

AN:

41376

Ashkenazi Jewish (ASJ)

AF:

0.00302

AC:

AN:

24804

East Asian (EAS)

AF:

0.196

AC:

7540

AN:

38390

South Asian (SAS)

AF:

0.00759

AC:

633

AN:

83348

European-Finnish (FIN)

AF:

0.0299

AC:

1581

AN:

52846

Middle Eastern (MID)

AF:

0.00213

AC:

AN:

5642

European-Non Finnish (NFE)

AF:

0.000674

AC:

737

AN:

1093666

Other (OTH)

AF:

0.0123

AC:

724

AN:

59018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

646

1291

1937

2582

3228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

352

528

704

880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0128

AC:

1953

AN:

152296

Hom.:

117

Cov.:

AF XY:

0.0156

AC XY:

1160

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000866

AC:

AN:

41570

American (AMR)

AF:

0.0233

AC:

356

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00346

AC:

AN:

3472

East Asian (EAS)

AF:

0.198

AC:

1023

AN:

5164

South Asian (SAS)

AF:

0.0149

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0322

AC:

342

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00131

AC:

AN:

68028

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

177

265

354

442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00319

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.0990

AC:

342

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jan 16, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 12, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Congenital muscular dystrophy with intellectual disability and severe epilepsy

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.7

(source)

DANN

Benign

0.71

PhyloP100

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over