Genetic Variant 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023935.3. 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
	DDRGK1	NM_023935.3	MANE Select	c.92-72G>A		intron	N/A	NP_076424.1	Q96HY6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDRGK1	ENST00000354488.8	TSL:1 MANE Select	c.92-72G>A	intron	N/A	ENSP00000346483.3	Q96HY6-1
DDRGK1	ENST00000897092.1		c.92-72G>A	intron	N/A	ENSP00000567151.1
DDRGK1	ENST00000941356.1		c.92-72G>A	intron	N/A	ENSP00000611415.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over