NM_005216.5:c.551+262A>C

Variant names:

• chr1-20655178-T-G
• rs710319
• NM_005216.5:c.551+262A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005216.5(DDOST):​c.551+262A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 148,166 control chromosomes in the GnomAD database, including 11,397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (11397 hom., cov: 27)
• Consequence: DDOST NM_005216.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.773
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-20655178-T-G is Benign according to our data. Variant chr1-20655178-T-G is described in ClinVar as Benign. ClinVar VariationId is 1262237.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005216.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDOST	NM_005216.5	MANE Select	c.551+262A>C		intron	N/A	NP_005207.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDOST	ENST00000602624.7	TSL:1 MANE Select	c.551+262A>C		intron	N/A	ENSP00000473655.2
	DDOST	ENST00000415136.6	TSL:1	c.602+262A>C		intron	N/A	ENSP00000399457.3

Frequencies

GnomAD3 genomes AF: 0.393 AC: 58123 AN: 148072 Hom.: 11388 Cov.: 27

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.392 AC: 58148 AN: 148166 Hom.: 11397 Cov.: 27 AF XY: 0.393 AC XY: 28335 AN XY: 72170

African (AFR) AF: 0.387 AC: 15546 AN: 40136

American (AMR) AF: 0.425 AC: 6311 AN: 14856

Ashkenazi Jewish (ASJ) AF: 0.429 AC: 1475 AN: 3442

East Asian (EAS) AF: 0.282 AC: 1395 AN: 4954

South Asian (SAS) AF: 0.308 AC: 1418 AN: 4600

European-Finnish (FIN) AF: 0.391 AC: 3815 AN: 9764

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

European-Non Finnish (NFE) AF: 0.401 AC: 26935 AN: 67176

Other (OTH) AF: 0.403 AC: 823 AN: 2042

Alfa AF: 0.175 Hom.: 259

Asia WGS AF: 0.302 AC: 1050 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 06, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.5
DANN	Benign	0.18
PhyloP100		0.77
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: rs710319; hg19: chr1-20981671;