rs986242989

Variant names:

• chr16-67990913-C-G
• rs986242989
• NM_022355.4:c.817G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-67990913-C-G
• chr16-67990913-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022355.4(DPEP2):​c.817G>C​(p.Val273Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. V273M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPEP2 NM_022355.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11633149).

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.817G>C	p.Val273Leu	missense	Exon 7 of 11	NP_071750.1	Q9H4A9-1
	DPEP2	NM_001369657.1		c.817G>C	p.Val273Leu	missense	Exon 6 of 10	NP_001356586.1	Q9H4A9-1
	DPEP2	NM_001324159.2		c.343G>C	p.Val115Leu	missense	Exon 5 of 9	NP_001311088.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPEP2	ENST00000393847.6	TSL:1 MANE Select	c.817G>C	p.Val273Leu	missense	Exon 7 of 11	ENSP00000377430.1	Q9H4A9-1
	DPEP2	ENST00000572888.5	TSL:1	c.817G>C	p.Val273Leu	missense	Exon 6 of 10	ENSP00000458977.1	Q9H4A9-1
	DPEP2	ENST00000867048.1		c.817G>C	p.Val273Leu	missense	Exon 7 of 11	ENSP00000537107.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.089	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L
PhyloP100		-0.57
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.022
Sift	Benign	0.24	T
Sift4G	Benign	0.25	T
Polyphen		0.0080	B
Vest4		0.044
MutPred		0.50		Gain of helix (P = 0.132)
MVP		0.13
ClinPred		0.092	T
GERP RS		3.1
Varity_R		0.065
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs986242989; hg19: chr16-68024816;