2-162074215-T-G

Variant names:

• chr2-162074215-T-G
• rs13015258
• NM_001935.4:c.-234A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DPP4	NM_001935.4	c.-234A>C		5_prime_UTR_variant	Exon 1 of 26	ENST00000360534.8	NP_001926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP4	ENST00000360534.8	c.-234A>C		5_prime_UTR_variant	Exon 1 of 26	1	NM_001935.4	ENSP00000353731.3

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

African (AFR) AF: 0.668 AC: 14583 AN: 21818

American (AMR) AF: 0.406 AC: 3108 AN: 7664

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 8248 AN: 13084

East Asian (EAS) AF: 0.306 AC: 7593 AN: 24806

South Asian (SAS) AF: 0.669 AC: 13285 AN: 19852

European-Finnish (FIN) AF: 0.509 AC: 10687 AN: 20982

Middle Eastern (MID) AF: 0.632 AC: 1748 AN: 2768

European-Non Finnish (NFE) AF: 0.617 AC: 561561 AN: 909832

Other (OTH) AF: 0.613 AC: 25801 AN: 42068

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

African (AFR) AF: 0.666 AC: 27587 AN: 41442

American (AMR) AF: 0.475 AC: 7249 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2247 AN: 3470

East Asian (EAS) AF: 0.396 AC: 2043 AN: 5154

South Asian (SAS) AF: 0.665 AC: 3207 AN: 4822

European-Finnish (FIN) AF: 0.496 AC: 5193 AN: 10460

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.606 AC: 41127 AN: 67876

Other (OTH) AF: 0.629 AC: 1326 AN: 2108

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
PhyloP100		-2.2
PromoterAI		0.0071	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13015258; hg19: chr2-162930725;