NM_001388.5:c.807-576C>T

Variant names:

• chr17-18103225-C-T
• rs854809
• NM_001388.5:c.807-576C>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.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
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.685 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.807-576C>T		intron	N/A	NP_001379.1
	DRG2	NM_001330144.2		c.807-576C>T		intron	N/A	NP_001317073.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRG2	ENST00000225729.8	TSL:1 MANE Select	c.807-576C>T		intron	N/A	ENSP00000225729.3
	DRG2	ENST00000395726.8	TSL:5	c.807-576C>T		intron	N/A	ENSP00000379076.4
	DRG2	ENST00000583355.1	TSL:3	c.226-576C>T		intron	N/A	ENSP00000463256.1

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

African (AFR) AF: 0.554 AC: 22941 AN: 41380

American (AMR) AF: 0.473 AC: 7205 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1438 AN: 3466

East Asian (EAS) AF: 0.651 AC: 3344 AN: 5138

South Asian (SAS) AF: 0.704 AC: 3381 AN: 4800

European-Finnish (FIN) AF: 0.416 AC: 4379 AN: 10536

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21832 AN: 67934

Other (OTH) AF: 0.412 AC: 869 AN: 2110

Alfa AF: 0.361 Hom.: 4070

Bravo AF: 0.439

Asia WGS AF: 0.651 AC: 2262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.74
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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