rs6781

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003863.4(DPM2):c.213T>C(p.Tyr71Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 1,610,162 control chromosomes in the GnomAD database, including 578,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 49374 hom., cov: 32)

Exomes 𝑓: 0.85 ( 528785 hom. )

Consequence

DPM2
NM_003863.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.13

Publications

33 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-127935764-A-G is Benign according to our data. Variant chr9-127935764-A-G is described in ClinVar as Benign. ClinVar VariationId is 128920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003863.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DPM2	NM_003863.4	MANE Select	c.213T>C	p.Tyr71Tyr	synonymous	Exon 4 of 4	NP_003854.1
DPM2	NM_001378437.1		c.123T>C	p.Tyr41Tyr	synonymous	Exon 3 of 3	NP_001365366.1
DPM2	NR_165631.1		n.370T>C		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DPM2	ENST00000314392.13	TSL:1 MANE Select	c.213T>C	p.Tyr71Tyr	synonymous	Exon 4 of 4	ENSP00000322181.8
DPM2	ENST00000470181.1	TSL:1	n.505T>C		non_coding_transcript_exon	Exon 3 of 3
DPM2	ENST00000495270.1	TSL:1	n.997T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.800

AC:

121591

AN:

151956

Hom.:

49343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.673

Gnomad AMI

AF:

0.919

Gnomad AMR

AF:

0.842

Gnomad ASJ

AF:

0.731

Gnomad EAS

AF:

0.654

Gnomad SAS

AF:

0.689

Gnomad FIN

AF:

0.902

Gnomad MID

AF:

0.752

Gnomad NFE

AF:

0.874

Gnomad OTH

AF:

0.793

GnomAD2 exomes

AF:

0.818

AC:

205198

AN:

250718

AF XY:

0.817

show subpopulations

Gnomad AFR exome

AF:

0.669

Gnomad AMR exome

AF:

0.873

Gnomad ASJ exome

AF:

0.734

Gnomad EAS exome

AF:

0.672

Gnomad FIN exome

AF:

0.896

Gnomad NFE exome

AF:

0.868

Gnomad OTH exome

AF:

0.817

GnomAD4 exome

AF:

0.849

AC:

1237344

AN:

1458086

Hom.:

528785

Cov.:

AF XY:

0.845

AC XY:

612769

AN XY:

725488

show subpopulations

African (AFR)

AF:

0.676

AC:

22540

AN:

33344

American (AMR)

AF:

0.869

AC:

38808

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.729

AC:

19011

AN:

26074

East Asian (EAS)

AF:

0.619

AC:

24531

AN:

39660

South Asian (SAS)

AF:

0.713

AC:

61368

AN:

86092

European-Finnish (FIN)

AF:

0.898

AC:

47884

AN:

53350

Middle Eastern (MID)

AF:

0.744

AC:

4284

AN:

5758

European-Non Finnish (NFE)

AF:

0.874

AC:

969398

AN:

1108904

Other (OTH)

AF:

0.822

AC:

49520

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.410

Heterozygous variant carriers

9610

19220

28830

38440

48050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21128

42256

63384

84512

105640

<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:

0.800

AC:

121671

AN:

152076

Hom.:

49374

Cov.:

AF XY:

0.798

AC XY:

59360

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.673

AC:

27885

AN:

41440

American (AMR)

AF:

0.842

AC:

12863

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.731

AC:

2538

AN:

3472

East Asian (EAS)

AF:

0.653

AC:

3369

AN:

5156

South Asian (SAS)

AF:

0.691

AC:

3331

AN:

4824

European-Finnish (FIN)

AF:

0.902

AC:

9564

AN:

10604

Middle Eastern (MID)

AF:

0.745

AC:

219

AN:

294

European-Non Finnish (NFE)

AF:

0.874

AC:

59388

AN:

67986

Other (OTH)

AF:

0.795

AC:

1676

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1170

2340

3510

4680

5850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

872

1744

2616

3488

4360

<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:

0.839

Hom.:

60639

Bravo

AF:

0.792

Asia WGS

AF:

0.715

AC:

2490

AN:

3478

EpiCase

AF:

0.856

EpiControl

AF:

0.856

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital muscular dystrophy with intellectual disability and severe epilepsy (4)

not specified (4)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.8

(source)

DANN

Benign

0.83

PhyloP100

-1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over