rs854813

Variant names:

• chr17-18100531-C-T
• rs854813
• NM_001388.5:c.541-38C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 22 publications found

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]

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 33

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

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.: 37 AF XY: 0.536 AC XY: 389597 AN XY: 726814

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

GnomAD4 genome AF: 0.434 AC: 66045 AN: 152106 Hom.: 16653 Cov.: 33 AF XY: 0.423 AC XY: 31472 AN XY: 74356

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

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
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)

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

Other links and lift over

dbSNP: rs854813; hg19: chr17-18003845; COSMIC: COSV56728455; COSMIC: COSV56728455;