rs7608798

Positions:

• chr2-162033707-G-A
• chr2-162033707-G-C
• chr2-162033707-G-T

Variant summary

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

The NM_001935.4(DPP4):​c.775-54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 1,202,210 control chromosomes in the GnomAD database, including 70,896 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 0.35 (9399 hom., cov: 26)
  • Exomes 𝑓: 0.33 (61497 hom.)
• Consequence: DPP4 NM_001935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.123

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP4	NM_001935.4	c.775-54C>T		intron_variant		ENST00000360534.8	NP_001926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP4	ENST00000360534.8	c.775-54C>T		intron_variant		1	NM_001935.4	ENSP00000353731	P3

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52018 AN: 148930 Hom.: 9399 Cov.: 26

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.327 AC: 344717 AN: 1053198 Hom.: 61497 AF XY: 0.325 AC XY: 174421 AN XY: 536054

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.415

Gnomad4 EAS exome AF: 0.710

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.309

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.349 AC: 52023 AN: 149012 Hom.: 9399 Cov.: 26 AF XY: 0.352 AC XY: 25552 AN XY: 72524

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.336

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.324

Gnomad4 OTH AF: 0.322

Alfa AF: 0.275 Hom.: 1192

Bravo AF: 0.351

Asia WGS AF: 0.399 AC: 1367 AN: 3430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.61

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: rs7608798; hg19: chr2-162890217; COSMIC: COSV62108770; COSMIC: COSV62108770;