rs976551789

Variant names:

• chr16-67990961-C-G
• rs976551789
• NM_022355.4:c.769G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-67990961-C-G
• chr16-67990961-C-T

Variant summary

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

The NM_022355.4(DPEP2):​c.769G>C​(p.Val257Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V257I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DPEP2 NM_022355.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.769G>C	p.Val257Leu	missense	Exon 7 of 11	NP_071750.1	Q9H4A9-1
	DPEP2	NM_001369657.1		c.769G>C	p.Val257Leu	missense	Exon 6 of 10	NP_001356586.1	Q9H4A9-1
	DPEP2	NM_001324159.2		c.295G>C	p.Val99Leu	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.769G>C	p.Val257Leu	missense	Exon 7 of 11	ENSP00000377430.1	Q9H4A9-1
	DPEP2	ENST00000572888.5	TSL:1	c.769G>C	p.Val257Leu	missense	Exon 6 of 10	ENSP00000458977.1	Q9H4A9-1
	DPEP2	ENST00000867048.1		c.769G>C	p.Val257Leu	missense	Exon 7 of 11	ENSP00000537107.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461852 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111980

Other (OTH) AF: 0.00 AC: 0 AN: 60394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.086	T
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0051	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-0.071
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.22
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.022	D
Polyphen		0.70	P
Vest4		0.30
MutPred		0.83		Loss of catalytic residue at V257 (P = 0.0577)
MVP		0.26
ClinPred		0.90	D
GERP RS		2.9
Varity_R		0.13
gMVP		0.62
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs976551789; hg19: chr16-68024864;