rs6781

Variant names:

• chr9-127935764-A-G
• rs6781
• NM_003863.4:c.213T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-127935764-A-G
• chr9-127935764-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: -1.13

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]

ENSG00000227218 (HGNC:):

ACMG classification

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 rank	MANE	Protein	UniProt
DPM2	NM_003863.4	c.213T>C	p.Tyr71Tyr	synonymous_variant	Exon 4 of 4	ENST00000314392.13	NP_003854.1
DPM2	NM_001378437.1	c.123T>C	p.Tyr41Tyr	synonymous_variant	Exon 3 of 3		NP_001365366.1
DPM2	NR_165631.1	n.370T>C		non_coding_transcript_exon_variant	Exon 4 of 4
DPM2	NR_165632.1	n.54T>C		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPM2	ENST00000314392.13	c.213T>C	p.Tyr71Tyr	synonymous_variant	Exon 4 of 4	1	NM_003863.4	ENSP00000322181.8

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121591 AN: 151956 Hom.: 49343 Cov.: 32

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

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.: 48 AF XY: 0.845 AC XY: 612769 AN XY: 725488

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.: 32 AF XY: 0.798 AC XY: 59360 AN XY: 74356

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:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Jan 05, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jan 16, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Congenital muscular dystrophy with intellectual disability and severe epilepsy Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Other links and lift over

dbSNP: rs6781; hg19: chr9-130698043; COSMIC: COSV58709132; COSMIC: COSV58709132;