chr9-127936566-C-T

Position:

chr9-127936566-C-T

Variant summary

Our verdict is Benign. Variant got -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

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:

DPM2 (HGNC:):

DPM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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/exons	MANE	Protein	UniProt
DPM2	NM_003863.4 linkuse as main transcript	c.183G>A	p.Leu61Leu	synonymous_variant	3/4	ENST00000314392.13	NP_003854.1	O94777
DPM2	NM_001378437.1 linkuse as main transcript	c.93G>A	p.Leu31Leu	synonymous_variant	2/3		NP_001365366.1
DPM2	NR_165631.1 linkuse as main transcript	n.340G>A		non_coding_transcript_exon_variant	3/4
DPM2	NR_165632.1 linkuse as main transcript	n.38-786G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPM2	ENST00000314392.13 linkuse as main transcript	c.183G>A	p.Leu61Leu	synonymous_variant	3/4	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

GnomAD3 exomes

AF:

0.0289

AC:

6716

AN:

232578

Hom.:

514

AF XY:

0.0257

AC XY:

3232

AN XY:

125926

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 SAS exome

AF:

0.00726

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

Gnomad4 AFR exome

AF:

0.000617

Gnomad4 AMR exome

AF:

0.0534

Gnomad4 ASJ exome

AF:

0.00302

Gnomad4 EAS exome

AF:

0.196

Gnomad4 SAS exome

AF:

0.00759

Gnomad4 FIN exome

AF:

0.0299

Gnomad4 NFE exome

AF:

0.000674

Gnomad4 OTH exome

AF:

0.0123

GnomAD4 genome

AF:

0.0128

AC:

1953

AN:

152296

Hom.:

117

Cov.:

AF XY:

0.0156

AC XY:

1160

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.0233

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.0149

Gnomad4 FIN

AF:

0.0322

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00296

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

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 12, 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	- -

Congenital muscular dystrophy with intellectual disability and severe epilepsy

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.7

DANN

Benign

0.71

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

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