rs6781

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003863.4(DPM2):c.213T>C(p.Tyr71=) 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:8

Conservation

PhyloP100: -1.13

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 128920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-127935764-A-G is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DPM2	NM_003863.4 linkuse as main transcript	c.213T>C	p.Tyr71=	synonymous_variant	4/4	ENST00000314392.13
DPM2	NM_001378437.1 linkuse as main transcript	c.123T>C	p.Tyr41=	synonymous_variant	3/3
DPM2	NR_165631.1 linkuse as main transcript	n.370T>C		non_coding_transcript_exon_variant	4/4
DPM2	NR_165632.1 linkuse as main transcript	n.54T>C		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPM2	ENST00000314392.13 linkuse as main transcript	c.213T>C	p.Tyr71=	synonymous_variant	4/4	1	NM_003863.4	P1
	ENST00000592240.5 linkuse as main transcript	n.143+1119A>G		intron_variant, non_coding_transcript_variant		5

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

GnomAD3 exomes

AF:

0.818

AC:

205198

AN:

250718

Hom.:

84941

AF XY:

0.817

AC XY:

110682

AN XY:

135526

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 SAS exome

AF:

0.712

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

Gnomad4 AFR exome

AF:

0.676

Gnomad4 AMR exome

AF:

0.869

Gnomad4 ASJ exome

AF:

0.729

Gnomad4 EAS exome

AF:

0.619

Gnomad4 SAS exome

AF:

0.713

Gnomad4 FIN exome

AF:

0.898

Gnomad4 NFE exome

AF:

0.874

Gnomad4 OTH exome

AF:

0.822

GnomAD4 genome

AF:

0.800

AC:

121671

AN:

152076

Hom.:

49374

Cov.:

AF XY:

0.798

AC XY:

59360

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.673

Gnomad4 AMR

AF:

0.842

Gnomad4 ASJ

AF:

0.731

Gnomad4 EAS

AF:

0.653

Gnomad4 SAS

AF:

0.691

Gnomad4 FIN

AF:

0.902

Gnomad4 NFE

AF:

0.874

Gnomad4 OTH

AF:

0.795

Alfa

AF:

0.841

Hom.:

51756

Bravo

AF:

0.792

Asia WGS

AF:

0.715

AC:

2490

AN:

3478

EpiCase

AF:

0.856

EpiControl

AF:

0.856

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 16, 2014	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Congenital muscular dystrophy with intellectual disability and severe epilepsy

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.8

DANN

Benign

0.83

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over