dbSNP rs2295553: DDRGK1:c.92-72G>A (chr20-3203488-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.101

Publications

15 publications found

Variant links:

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]

DDRGK1 Gene-Disease associations (from GenCC):

spondyloepimetaphyseal dysplasia, Shohat type
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

DDRGK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DDRGK1	NM_023935.3 link	c.92-72G>A		intron_variant	Intron 1 of 8	ENST00000354488.8	NP_076424.1	Q96HY6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDRGK1	ENST00000354488.8 link	c.92-72G>A		intron_variant	Intron 1 of 8	1	NM_023935.3	ENSP00000346483.3		Q96HY6-1
DDRGK1	ENST00000380201.2 link	c.92-72G>A		intron_variant	Intron 1 of 6	2		ENSP00000369548.2		A0A0A0MRX2

Frequencies

GnomAD3 genomes

AF:

0.530

AC:

80556

AN:

152036

Hom.:

21735

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.632

AC:

17357

AN:

27448

American (AMR)

AF:

0.441

AC:

7871

AN:

17866

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

8764

AN:

18402

East Asian (EAS)

AF:

0.451

AC:

14730

AN:

32630

South Asian (SAS)

AF:

0.517

AC:

31632

AN:

61146

European-Finnish (FIN)

AF:

0.408

AC:

18115

AN:

44384

Middle Eastern (MID)

AF:

0.503

AC:

2209

AN:

4388

European-Non Finnish (NFE)

AF:

0.518

AC:

529277

AN:

1022652

Other (OTH)

AF:

0.516

AC:

27152

AN:

52642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

16780

33560

50341

67121

83901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16172

32344

48516

64688

80860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.530

AC:

80627

AN:

152154

Hom.:

21764

Cov.:

AF XY:

0.523

AC XY:

38898

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.626

AC:

26018

AN:

41542

American (AMR)

AF:

0.466

AC:

7117

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.479

AC:

1659

AN:

3466

East Asian (EAS)

AF:

0.432

AC:

2228

AN:

5156

South Asian (SAS)

AF:

0.527

AC:

2541

AN:

4826

European-Finnish (FIN)

AF:

0.394

AC:

4168

AN:

10588

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.516

AC:

35075

AN:

67980

Other (OTH)

AF:

0.555

AC:

1173

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1977

3954

5931

7908

9885

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.518

Hom.:

5646

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

(source)

DANN

Benign

0.89

PhyloP100

-0.10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over