11-119097569-C-T

Variant names:

• chr11-119097569-C-T
• rs145206990
• NM_001382.4:c.918-18G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001382.4(DPAGT1):​c.918-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,696 control chromosomes in the GnomAD database, including 207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0083 (4 hom., cov: 32)
  • Exomes 𝑓: 0.014 (203 hom.)
• Consequence: DPAGT1 NM_001382.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.0830
• Publications: 2 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), Genomics England PanelApp, G2P
• DPAGT1-congenital disorder of glycosylation

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 11-119097569-C-T is Benign according to our data. Variant chr11-119097569-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00834 (1270/152272) while in subpopulation NFE AF = 0.0153 (1042/68024). AF 95% confidence interval is 0.0145. There are 4 homozygotes in GnomAd4. There are 533 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPAGT1	NM_001382.4	MANE Select	c.918-18G>A		intron	N/A	NP_001373.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPAGT1	ENST00000354202.9	TSL:1 MANE Select	c.918-18G>A		intron	N/A	ENSP00000346142.4	Q9H3H5-1
	DPAGT1	ENST00000409993.6	TSL:2	c.918-18G>A		intron	N/A	ENSP00000386597.2	Q9H3H5-1
	DPAGT1	ENST00000867497.1		c.918-18G>A		intron	N/A	ENSP00000537556.1

Frequencies

GnomAD3 genomes AF: 0.00835 AC: 1270 AN: 152154 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00328

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00341

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.00575

GnomAD2 exomes AF: 0.00787 AC: 1979 AN: 251452 AF XY: 0.00799

Gnomad AFR exome AF: 0.00234

Gnomad AMR exome AF: 0.00332

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00171

Gnomad NFE exome AF: 0.0143

Gnomad OTH exome AF: 0.00831

GnomAD4 exome AF: 0.0144 AC: 20987 AN: 1461424 Hom.: 203 Cov.: 33 AF XY: 0.0139 AC XY: 10124 AN XY: 727046

African (AFR) AF: 0.00218 AC: 73 AN: 33478

American (AMR) AF: 0.00351 AC: 157 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 18 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00395 AC: 341 AN: 86250

European-Finnish (FIN) AF: 0.00208 AC: 111 AN: 53400

Middle Eastern (MID) AF: 0.00208 AC: 12 AN: 5768

European-Non Finnish (NFE) AF: 0.0176 AC: 19523 AN: 1111592

Other (OTH) AF: 0.0124 AC: 751 AN: 60378

GnomAD4 genome AF: 0.00834 AC: 1270 AN: 152272 Hom.: 4 Cov.: 32 AF XY: 0.00716 AC XY: 533 AN XY: 74454

African (AFR) AF: 0.00327 AC: 136 AN: 41556

American (AMR) AF: 0.00340 AC: 52 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4822

European-Finnish (FIN) AF: 0.000660 AC: 7 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0153 AC: 1042 AN: 68024

Other (OTH) AF: 0.00569 AC: 12 AN: 2110

Alfa AF: 0.00998 Hom.: 3

Bravo AF: 0.00850

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	DPAGT1-congenital disorder of glycosylation;C3553645:Congenital myasthenic syndrome 13 (2)
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.57
PhyloP100		0.083
Mutation Taster		=100/0	polymorphism

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: rs145206990; hg19: chr11-118968279;