17-18103225-C-T

Position:

• chr17-18103225-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.807-576C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,812 control chromosomes in the GnomAD database, including 15,401 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 (15401 hom., cov: 31)
• Consequence: DRG2 NM_001388.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.383

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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRG2	NM_001388.5	c.807-576C>T		intron_variant		ENST00000225729.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRG2	ENST00000225729.8	c.807-576C>T		intron_variant		1	NM_001388.5	P1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65811 AN: 151694 Hom.: 15373 Cov.: 31

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.704

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.412

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.434 AC: 65882 AN: 151812 Hom.: 15401 Cov.: 31 AF XY: 0.444 AC XY: 32938 AN XY: 74154

Gnomad4 AFR AF: 0.554

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.412

Alfa AF: 0.358 Hom.: 3944

Bravo AF: 0.439

Asia WGS AF: 0.651 AC: 2262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.74

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: rs854809; hg19: chr17-18006539; COSMIC: COSV56729339; COSMIC: COSV56729339;