16-67987873-CC-TT

Variant names:

• chr16-67987873-CC-TT
• NM_022355.4:c.1184_1185delGGinsAA
• DPEP2 p.Arg395Gln

Variant summary

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

The NM_022355.4(DPEP2):​c.1184_1185delGGinsAA​(p.Arg395Gln) variant causes a missense change. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPEP2 NM_022355.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.33
• Publications: 0 publications found

Genes affected

DPEP2 (HGNC:23028): (dipeptidase 2) DPEP2 belongs to the membrane-bound dipeptidase (EC 3.4.13.19) family. These enzymes hydrolyze a variety of dipeptides, including leukotriene D4, the beta-lactam ring of some antibiotics, and cystinyl-bis-glycine (cys-bis-gly) formed during glutathione degradation (Habib et al., 2003 [PubMed 12738806]).[supplied by OMIM, Mar 2008]

DUS2 (HGNC:26014): (dihydrouridine synthase 2) This gene encodes a cytoplasmic protein that catalyzes the conversion of uridine residues to dihydrouridine in the D-loop of tRNA. The resulting modified bases confer enhanced regional flexibility to tRNA. The encoded protein may increase the rate of translation by inhibiting an interferon-induced protein kinase. This gene has been implicated in pulmonary carcinogenesis. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022355.4. 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
	DPEP2	NM_022355.4	MANE Select	c.1184_1185delGGinsAA	p.Arg395Gln	missense	N/A	NP_071750.1	Q9H4A9-1
	DPEP2	NM_001369657.1		c.1184_1185delGGinsAA	p.Arg395Gln	missense	N/A	NP_001356586.1	Q9H4A9-1
	DPEP2	NM_001324159.2		c.710_711delGGinsAA	p.Arg237Gln	missense	N/A	NP_001311088.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPEP2	ENST00000393847.6	TSL:1 MANE Select	c.1184_1185delGGinsAA	p.Arg395Gln	missense	N/A	ENSP00000377430.1	Q9H4A9-1
	DPEP2	ENST00000572888.5	TSL:1	c.1184_1185delGGinsAA	p.Arg395Gln	missense	N/A	ENSP00000458977.1	Q9H4A9-1
	DPEP2	ENST00000867048.1		c.1223_1224delGGinsAA	p.Arg408Gln	missense	N/A	ENSP00000537107.1

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		6.3

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: chr16-68021776;