rs640742

Variant names:

• chr1-20658061-A-C
• rs640742
• NM_005216.5:c.266-1874T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-20658061-A-C
• chr1-20658061-A-G
• chr1-20658061-A-T

Variant summary

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

The NM_005216.5(DDOST):​c.266-1874T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,164 control chromosomes in the GnomAD database, including 11,323 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 (11323 hom., cov: 33)
• Consequence: DDOST NM_005216.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 13 publications found

Genes affected

DDOST (HGNC:2728): (dolichyl-diphosphooligosaccharide--protein glycosyltransferase non-catalytic subunit) This gene encodes a component of the oligosaccharyltransferase complex which catalyzes the transfer of high-mannose oligosaccharides to asparagine residues on nascent polypeptides in the lumen of the rough endoplasmic reticulum. The protein complex co-purifies with ribosomes. The product of this gene is also implicated in the processing of advanced glycation endproducts (AGEs), which form from non-enzymatic reactions between sugars and proteins or lipids and are associated with aging and hyperglycemia. [provided by RefSeq, Jul 2008]

DDOST Gene-Disease associations (from GenCC):

• DDOST-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDOST	NM_005216.5	c.266-1874T>G		intron_variant	Intron 2 of 10	ENST00000602624.7	NP_005207.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDOST	ENST00000602624.7	c.266-1874T>G		intron_variant	Intron 2 of 10	1	NM_005216.5	ENSP00000473655.2
DDOST	ENST00000415136.6	c.317-1874T>G		intron_variant	Intron 2 of 10	1		ENSP00000399457.3
DDOST	ENST00000464364.1	c.266-2282T>G		intron_variant	Intron 2 of 3	5		ENSP00000475634.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58586 AN: 152046 Hom.: 11320 Cov.: 33

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.396

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.385 AC: 58614 AN: 152164 Hom.: 11323 Cov.: 33 AF XY: 0.386 AC XY: 28684 AN XY: 74392

African (AFR) AF: 0.366 AC: 15171 AN: 41504

American (AMR) AF: 0.416 AC: 6371 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1485 AN: 3472

East Asian (EAS) AF: 0.280 AC: 1450 AN: 5180

South Asian (SAS) AF: 0.304 AC: 1468 AN: 4826

European-Finnish (FIN) AF: 0.387 AC: 4096 AN: 10590

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27311 AN: 67982

Other (OTH) AF: 0.393 AC: 828 AN: 2108

Alfa AF: 0.373 Hom.: 6156

Bravo AF: 0.386

Asia WGS AF: 0.311 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.73
PhyloP100		-0.18
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: rs640742; hg19: chr1-20984554; COSMIC: COSV66718271; COSMIC: COSV66718271;