rs11552794

chr9-127936566-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003863.4(DPM2):c.183G>A(p.Leu61=) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.23

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]

(HGNC:):

ACMG classification

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	UniProt
DPM2	NM_003863.4	c.183G>A	p.Leu61=	synonymous_variant	3/4	ENST00000314392.13
DPM2	NM_001378437.1	c.93G>A	p.Leu31=	synonymous_variant	2/3
DPM2	NR_165631.1	n.340G>A		non_coding_transcript_exon_variant	3/4
DPM2	NR_165632.1	n.38-786G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPM2	ENST00000314392.13	c.183G>A	p.Leu61=	synonymous_variant	3/4	1	NM_003863.4	P1
	ENST00000592240.5	n.143+1921C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1960 AN: 152178 Hom.: 117 Cov.: 33

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

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.: 30 AF XY: 0.00922 AC XY: 6536 AN XY: 708634

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.: 33 AF XY: 0.0156 AC XY: 1160 AN XY: 74460

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.: 1

Bravo AF: 0.0145

Asia WGS AF: 0.0990 AC: 342 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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. -
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	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	Invitae	Jan 31, 2024	- -

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

Other links and lift over

dbSNP: rs11552794; hg19: chr9-130698845; COSMIC: COSV55948109; COSMIC: COSV55948109;