Genetic Variant DRG2:c.541-38C>T (chr17-18100531-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_001388.5(DRG2):c.541-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 1,613,028 control chromosomes in the GnomAD database, including 246,822 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 0.43 ( 16653 hom., cov: 33)

Exomes 𝑓: 0.54 ( 230169 hom. )

Consequence

DRG2
NM_001388.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.95

Publications

22 publications found

Variant links:

Genes affected

DRG2 (HGNC:3030): (developmentally regulated GTP binding protein 2) This gene encodes a GTP-binding protein known to function in the regulation of cell growth and differentiation. Read-through transcripts containing this gene and a downstream gene have been identified, but they are not thought to encode a fusion protein. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jan 2012]

DRG2 links:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001388.5. 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
	DRG2	NM_001388.5	MANE Select	c.541-38C>T		intron	N/A	NP_001379.1	P55039
	DRG2	NM_001330144.2		c.541-38C>T		intron	N/A	NP_001317073.1	A8MZF9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DRG2	ENST00000225729.8	TSL:1 MANE Select	c.541-38C>T	intron	N/A	ENSP00000225729.3	P55039
DRG2	ENST00000864168.1		c.541-38C>T	intron	N/A	ENSP00000534227.1
DRG2	ENST00000968692.1		c.583-38C>T	intron	N/A	ENSP00000638751.1

Frequencies

GnomAD3 genomes

AF:

0.434

AC:

66019

AN:

151988

Hom.:

16644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.529

Gnomad AMR

AF:

0.416

Gnomad ASJ

AF:

0.508

Gnomad EAS

AF:

0.0683

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.467

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.467

GnomAD2 exomes

AF:

0.438

AC:

109815

AN:

250822

AF XY:

0.439

show subpopulations

Gnomad AFR exome

AF:

0.222

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.509

Gnomad EAS exome

AF:

0.0674

Gnomad FIN exome

AF:

0.488

Gnomad NFE exome

AF:

0.589

Gnomad OTH exome

AF:

0.483

GnomAD4 exome

AF:

0.544

AC:

794799

AN:

1460922

Hom.:

230169

Cov.:

AF XY:

0.536

AC XY:

389597

AN XY:

726814

show subpopulations

African (AFR)

AF:

0.213

AC:

7142

AN:

33454

American (AMR)

AF:

0.359

AC:

16015

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.507

AC:

13257

AN:

26132

East Asian (EAS)

AF:

0.0712

AC:

2827

AN:

39692

South Asian (SAS)

AF:

0.248

AC:

21402

AN:

86230

European-Finnish (FIN)

AF:

0.500

AC:

26708

AN:

53378

Middle Eastern (MID)

AF:

0.467

AC:

2695

AN:

5768

European-Non Finnish (NFE)

AF:

0.607

AC:

674317

AN:

1111224

Other (OTH)

AF:

0.504

AC:

30436

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

20164

40328

60491

80655

100819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17818

35636

53454

71272

89090

<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:

0.434

AC:

66045

AN:

152106

Hom.:

16653

Cov.:

AF XY:

0.423

AC XY:

31472

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.231

AC:

9569

AN:

41482

American (AMR)

AF:

0.416

AC:

6358

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.508

AC:

1761

AN:

3468

East Asian (EAS)

AF:

0.0682

AC:

353

AN:

5174

South Asian (SAS)

AF:

0.243

AC:

1171

AN:

4826

European-Finnish (FIN)

AF:

0.467

AC:

4940

AN:

10586

Middle Eastern (MID)

AF:

0.524

AC:

153

AN:

292

European-Non Finnish (NFE)

AF:

0.593

AC:

40273

AN:

67970

Other (OTH)

AF:

0.467

AC:

986

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1744

3488

5232

6976

8720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.541

Hom.:

42394

Bravo

AF:

0.423

Asia WGS

AF:

0.210

AC:

735

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.15

(source)

DANN

Benign

0.66

PhyloP100

-1.9

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)

0.010

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