11-119096814-C-T

Variant names:

• chr11-119096814-C-T
• rs8551
• NM_001382.4:c.*184G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382.4(DPAGT1):​c.*184G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 719,004 control chromosomes in the GnomAD database, including 66,477 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.39 (12042 hom., cov: 32)
  • Exomes 𝑓: 0.43 (54435 hom.)
• Consequence: DPAGT1 NM_001382.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.195
• Publications: 21 publications found

Genes affected

DPAGT1 (HGNC:2995): (dolichyl-phosphate N-acetylglucosaminephosphotransferase 1) The protein encoded by this gene is an enzyme that catalyzes the first step in the dolichol-linked oligosaccharide pathway for glycoprotein biosynthesis. This enzyme belongs to the glycosyltransferase family 4. This protein is an integral membrane protein of the endoplasmic reticulum. The congenital disorder of glycosylation type Ij is caused by mutation in the gene encoding this enzyme. [provided by RefSeq, Jul 2008]

DPAGT1 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 13

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, G2P
• DPAGT1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, G2P
• congenital myasthenic syndromes with glycosylation defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPAGT1	NM_001382.4	c.*184G>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000354202.9	NP_001373.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPAGT1	ENST00000354202.9	c.*184G>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_001382.4	ENSP00000346142.4

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58869 AN: 151786 Hom.: 12031 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.421

GnomAD4 exome AF: 0.430 AC: 243846 AN: 567100 Hom.: 54435 Cov.: 7 AF XY: 0.436 AC XY: 130835 AN XY: 300336

African (AFR) AF: 0.285 AC: 4295 AN: 15076

American (AMR) AF: 0.271 AC: 7619 AN: 28120

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 9282 AN: 16872

East Asian (EAS) AF: 0.621 AC: 19749 AN: 31796

South Asian (SAS) AF: 0.498 AC: 26969 AN: 54148

European-Finnish (FIN) AF: 0.384 AC: 14247 AN: 37110

Middle Eastern (MID) AF: 0.466 AC: 1083 AN: 2324

European-Non Finnish (NFE) AF: 0.419 AC: 147391 AN: 351412

Other (OTH) AF: 0.437 AC: 13211 AN: 30242

GnomAD4 genome AF: 0.388 AC: 58905 AN: 151904 Hom.: 12042 Cov.: 32 AF XY: 0.390 AC XY: 28980 AN XY: 74240

African (AFR) AF: 0.290 AC: 11986 AN: 41388

American (AMR) AF: 0.328 AC: 5009 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1851 AN: 3466

East Asian (EAS) AF: 0.642 AC: 3306 AN: 5146

South Asian (SAS) AF: 0.516 AC: 2486 AN: 4822

European-Finnish (FIN) AF: 0.393 AC: 4154 AN: 10560

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.422 AC: 28650 AN: 67950

Other (OTH) AF: 0.425 AC: 897 AN: 2112

Alfa AF: 0.398 Hom.: 7709

Bravo AF: 0.378

Asia WGS AF: 0.542 AC: 1889 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Congenital disorder of glycosylation Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Acute intermittent porphyria Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

DPAGT1-congenital disorder of glycosylation Benign:1

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.26
DANN	Benign	0.36
PhyloP100		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8551; hg19: chr11-118967524; COSMIC: COSV53830464; COSMIC: COSV53830464;