rs854813

Positions:

• chr17-18100531-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRG2	NM_001388.5	c.541-38C>T		intron_variant		ENST00000225729.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRG2	ENST00000225729.8	c.541-38C>T		intron_variant		1	NM_001388.5	P1

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

GnomAD3 exomes AF: 0.438 AC: 109815 AN: 250822 Hom.: 27775 AF XY: 0.439 AC XY: 59573 AN XY: 135574

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 SAS exome AF: 0.245

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

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.0712

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.607

Gnomad4 OTH exome AF: 0.504

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

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.0682

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.467

Alfa AF: 0.551 Hom.: 35228

Bravo AF: 0.423

Asia WGS AF: 0.210 AC: 735 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.15
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

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