rs13015258

Positions:

• chr2-162074215-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001935.4(DPP4):​c.-234A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,214,674 control chromosomes in the GnomAD database, including 226,495 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.60 (27745 hom., cov: 33)
  • Exomes 𝑓: 0.61 (198750 hom.)
• Consequence: DPP4 NM_001935.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16

Genes affected

DPP4 (HGNC:3009): (dipeptidyl peptidase 4) The DPP4 gene encodes dipeptidyl peptidase 4, which is identical to adenosine deaminase complexing protein-2, and to the T-cell activation antigen CD26. It is an intrinsic type II transmembrane glycoprotein and a serine exopeptidase that cleaves X-proline dipeptides from the N-terminus of polypeptides. Dipeptidyl peptidase 4 is highly involved in glucose and insulin metabolism, as well as in immune regulation. This protein was shown to be a functional receptor for Middle East respiratory syndrome coronavirus (MERS-CoV), and protein modeling suggests that it may play a similar role with SARS-CoV-2, the virus responsible for COVID-19. [provided by RefSeq, Apr 2020]

DPP4-DT (HGNC:40191): (DPP4 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP4	NM_001935.4	c.-234A>C		5_prime_UTR_variant	1/26	ENST00000360534.8	NP_001926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP4	ENST00000360534.8	c.-234A>C		5_prime_UTR_variant	1/26	1	NM_001935.4	ENSP00000353731	P3
DPP4-DT	ENST00000693081.1	n.158-569T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90732 AN: 151692 Hom.: 27711 Cov.: 33

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.627

GnomAD4 exome AF: 0.608 AC: 646614 AN: 1062874 Hom.: 198750 Cov.: 34 AF XY: 0.608 AC XY: 305657 AN XY: 502744

Gnomad4 AFR exome AF: 0.668

Gnomad4 AMR exome AF: 0.406

Gnomad4 ASJ exome AF: 0.630

Gnomad4 EAS exome AF: 0.306

Gnomad4 SAS exome AF: 0.669

Gnomad4 FIN exome AF: 0.509

Gnomad4 NFE exome AF: 0.617

Gnomad4 OTH exome AF: 0.613

GnomAD4 genome AF: 0.598 AC: 90802 AN: 151800 Hom.: 27745 Cov.: 33 AF XY: 0.591 AC XY: 43870 AN XY: 74192

Gnomad4 AFR AF: 0.666

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.606

Gnomad4 OTH AF: 0.629

Alfa AF: 0.603 Hom.: 3490

Bravo AF: 0.596

Asia WGS AF: 0.564 AC: 1955 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs13015258; hg19: chr2-162930725;