rs2295553

Positions:

• chr20-3203488-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_023935.3(DDRGK1):​c.92-72G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,433,712 control chromosomes in the GnomAD database, including 191,646 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 0.53 (21764 hom., cov: 33)
  • Exomes 𝑓: 0.51 (169882 hom.)
• Consequence: DDRGK1 NM_023935.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

Genes affected

DDRGK1 (HGNC:16110): (DDRGK domain containing 1) The protein encoded by this gene interacts with components of the ubiquitin fold modifier 1 conjugation pathway and helps prevent apoptosis in ER-stressed secretory tissues. In addition, the encoded protein regulates nuclear factor-κB activity. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDRGK1	NM_023935.3	c.92-72G>A		intron_variant		ENST00000354488.8	NP_076424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDRGK1	ENST00000354488.8	c.92-72G>A		intron_variant		1	NM_023935.3	ENSP00000346483	P1
DDRGK1	ENST00000380201.2	c.92-72G>A		intron_variant		2		ENSP00000369548

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80556 AN: 152036 Hom.: 21735 Cov.: 33

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.553

GnomAD4 exome AF: 0.513 AC: 657107 AN: 1281558 Hom.: 169882 AF XY: 0.511 AC XY: 317546 AN XY: 620820

Gnomad4 AFR exome AF: 0.632

Gnomad4 AMR exome AF: 0.441

Gnomad4 ASJ exome AF: 0.476

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.517

Gnomad4 FIN exome AF: 0.408

Gnomad4 NFE exome AF: 0.518

Gnomad4 OTH exome AF: 0.516

GnomAD4 genome AF: 0.530 AC: 80627 AN: 152154 Hom.: 21764 Cov.: 33 AF XY: 0.523 AC XY: 38898 AN XY: 74370

Gnomad4 AFR AF: 0.626

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.479

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.555

Alfa AF: 0.513 Hom.: 4934

Bravo AF: 0.535

Asia WGS AF: 0.555 AC: 1931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.0
DANN	Benign	0.89
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2295553; hg19: chr20-3184134; COSMIC: COSV63226631;