rs147263320

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_003863.4(DPM2):c.154G>A(p.Ala52Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,553,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

DPM2
NM_003863.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:4

Conservation

PhyloP100: 0.577

Publications

3 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: Orphanet, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

DPM2 links:

ENSG00000227218 (HGNC:):

ENSG00000227218 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055664867).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000158 (24/152202) while in subpopulation NFE AF = 0.000294 (20/68006). AF 95% confidence interval is 0.000194. There are 0 homozygotes in GnomAd4. There are 9 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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	UniProt
DPM2	NM_003863.4	MANE Select	c.154G>A	p.Ala52Thr	missense	Exon 3 of 4	NP_003854.1	O94777
DPM2	NM_001378437.1		c.64G>A	p.Ala22Thr	missense	Exon 2 of 3	NP_001365366.1
DPM2	NR_165631.1		n.311G>A		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPM2	ENST00000314392.13	TSL:1 MANE Select	c.154G>A	p.Ala52Thr	missense	Exon 3 of 4	ENSP00000322181.8	O94777
DPM2	ENST00000470181.1	TSL:1	n.446G>A		non_coding_transcript_exon	Exon 2 of 3
DPM2	ENST00000495270.1	TSL:1	n.938G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000258

AC:

AN:

205652

AF XY:

0.000217

show subpopulations

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:

0.000155

Gnomad NFE exome

AF:

0.000519

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000260

AC:

364

AN:

1401578

Hom.:

Cov.:

AF XY:

0.000218

AC XY:

151

AN XY:

691252

show subpopulations

African (AFR)

AF:

0.000160

AC:

AN:

31284

American (AMR)

AF:

0.00

AC:

AN:

36512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22730

East Asian (EAS)

AF:

0.00

AC:

AN:

37850

South Asian (SAS)

AF:

0.00

AC:

AN:

78494

European-Finnish (FIN)

AF:

0.000270

AC:

AN:

51790

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5400

European-Non Finnish (NFE)

AF:

0.000306

AC:

330

AN:

1079800

Other (OTH)

AF:

0.000260

AC:

AN:

57718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000158

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0000963

AC:

AN:

41526

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000192

Hom.:

Bravo

AF:

0.000144

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000305

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital muscular dystrophy with intellectual disability and severe epilepsy (2)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.13

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.77

M_CAP

Benign

0.026

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.96

PhyloP100

0.58

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.89

REVEL

Benign

0.093

Sift

Benign

0.31

Sift4G

Benign

0.33

Polyphen

0.0020

Vest4

0.16

MVP

0.52

MPC

0.60

ClinPred

0.055

GERP RS

-0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.069

gMVP

0.35

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

Other links and lift over