16-67990913-C-T

Variant names:

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

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>A​(p.Val273Met) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPEP2 NM_022355.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.1483261).

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>A	p.Val273Met	missense	Exon 7 of 11	NP_071750.1	Q9H4A9-1
	DPEP2	NM_001369657.1		c.817G>A	p.Val273Met	missense	Exon 6 of 10	NP_001356586.1	Q9H4A9-1
	DPEP2	NM_001324159.2		c.343G>A	p.Val115Met	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>A	p.Val273Met	missense	Exon 7 of 11	ENSP00000377430.1	Q9H4A9-1
	DPEP2	ENST00000572888.5	TSL:1	c.817G>A	p.Val273Met	missense	Exon 6 of 10	ENSP00000458977.1	Q9H4A9-1
	DPEP2	ENST00000867048.1		c.817G>A	p.Val273Met	missense	Exon 7 of 11	ENSP00000537107.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.054	N
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.57
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.037
Sift	Benign	0.050	D
Sift4G	Benign	0.12	T
Polyphen		0.22	B
Vest4		0.071
MutPred		0.42		Gain of disorder (P = 0.1211)
MVP		0.18
ClinPred		0.23	T
GERP RS		3.1
Varity_R		0.080
gMVP		0.40

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;