17-18093860-CGG-TTA

Variant names:

• chr17-18093860-CGG-TTA
• NM_001388.5:c.112_114delCGGinsTTA
• DRG2 p.Arg38Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001388.5(DRG2):​c.112_114delCGGinsTTA​(p.Arg38Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R38Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DRG2 NM_001388.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.88
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.112_114delCGGinsTTA	p.Arg38Leu	missense	N/A	NP_001379.1	P55039
	DRG2	NM_001330144.2		c.112_114delCGGinsTTA	p.Arg38Leu	missense	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.112_114delCGGinsTTA	p.Arg38Leu	missense	N/A	ENSP00000225729.3	P55039
	DRG2	ENST00000864168.1		c.112_114delCGGinsTTA	p.Arg38Leu	missense	N/A	ENSP00000534227.1
	DRG2	ENST00000968692.1		c.112_114delCGGinsTTA	p.Arg38Leu	missense	N/A	ENSP00000638751.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-17997174;