17-18098365-TG-T

Position:

• chr17-18098365-TG-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001388.5(DRG2):​c.315+9del variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,613,236 control chromosomes in the GnomAD database, including 8 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (8 hom.)
• Consequence: DRG2 NM_001388.5 splice_region, intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -1.10

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRG2	NM_001388.5	c.315+9del		splice_region_variant, intron_variant		ENST00000225729.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRG2	ENST00000225729.8	c.315+9del		splice_region_variant, intron_variant		1	NM_001388.5	P1

Frequencies

GnomAD3 genomes AF: 0.00191 AC: 291 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00353

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00197 AC: 494 AN: 251390 Hom.: 1 AF XY: 0.00194 AC XY: 264 AN XY: 135864

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00147

Gnomad FIN exome AF: 0.000970

Gnomad NFE exome AF: 0.00329

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00322 AC: 4708 AN: 1460932 Hom.: 8 Cov.: 29 AF XY: 0.00314 AC XY: 2282 AN XY: 726848

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.000783

Gnomad4 ASJ exome AF: 0.00142

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00124

Gnomad4 FIN exome AF: 0.000918

Gnomad4 NFE exome AF: 0.00383

Gnomad4 OTH exome AF: 0.00341

GnomAD4 genome AF: 0.00192 AC: 292 AN: 152304 Hom.: 0 Cov.: 32 AF XY: 0.00179 AC XY: 133 AN XY: 74482

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00353

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00301 Hom.: 1

Bravo AF: 0.00193

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00403

EpiControl AF: 0.00397

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

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Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs576131367; hg19: chr17-18001679;