dbSNP rs854762: DRG2:c.955-645G>A (chr17-18105788-G-A) – 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.955-645G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,466 control chromosomes in the GnomAD database, including 16,391 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 ( 16342 hom., cov: 33)

Exomes 𝑓: 0.51 ( 49 hom. )

Consequence

DRG2
NM_001388.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00900

Publications

8 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:

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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.587 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRG2	NM_001388.5	MANE Select	c.955-645G>A		intron	N/A	NP_001379.1
	DRG2	NM_001330144.2		c.955-645G>A		intron	N/A	NP_001317073.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DRG2	ENST00000225729.8	TSL:1 MANE Select	c.955-645G>A	intron	N/A	ENSP00000225729.3
DRG2	ENST00000482564.1	TSL:2	n.342G>A	non_coding_transcript_exon	Exon 1 of 2
DRG2	ENST00000395726.8	TSL:5	c.955-645G>A	intron	N/A	ENSP00000379076.4

Frequencies

GnomAD3 genomes

AF:

0.427

AC:

64845

AN:

151956

Hom.:

16333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.526

Gnomad AMR

AF:

0.412

Gnomad ASJ

AF:

0.506

Gnomad EAS

AF:

0.0683

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.466

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.592

Gnomad OTH

AF:

0.458

GnomAD4 exome

AF:

0.510

AC:

200

AN:

392

Hom.:

Cov.:

AF XY:

0.549

AC XY:

124

AN XY:

226

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AF:

0.240

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.375

AC:

AN:

European-Finnish (FIN)

AF:

0.700

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.559

AC:

152

AN:

272

Other (OTH)

AF:

0.583

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.427

AC:

64870

AN:

152074

Hom.:

16342

Cov.:

AF XY:

0.415

AC XY:

30869

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.206

AC:

8549

AN:

41480

American (AMR)

AF:

0.412

AC:

6291

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.506

AC:

1757

AN:

3472

East Asian (EAS)

AF:

0.0683

AC:

353

AN:

5172

South Asian (SAS)

AF:

0.242

AC:

1166

AN:

4818

European-Finnish (FIN)

AF:

0.466

AC:

4924

AN:

10574

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.592

AC:

40237

AN:

67960

Other (OTH)

AF:

0.458

AC:

969

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1670

3340

5009

6679

8349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<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:

0.527

Hom.:

10508

Bravo

AF:

0.414

Asia WGS

AF:

0.209

AC:

729

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.1

(source)

DANN

Benign

0.74

PhyloP100

0.0090

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