2-162059903-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.95-12402C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0415 in 152,248 control chromosomes in the GnomAD database, including 427 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 0.042 (427 hom., cov: 33)
• Consequence: DPP4 NM_001935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP4	NM_001935.4	c.95-12402C>A		intron_variant		ENST00000360534.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP4	ENST00000360534.8	c.95-12402C>A		intron_variant		1	NM_001935.4	P3

Frequencies

GnomAD3 genomes AF: 0.0415 AC: 6317 AN: 152130 Hom.: 425 Cov.: 33

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0150

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0202

Gnomad OTH AF: 0.0372

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0415 AC: 6319 AN: 152248 Hom.: 427 Cov.: 33 AF XY: 0.0487 AC XY: 3624 AN XY: 74434

Gnomad4 AFR AF: 0.0261

Gnomad4 AMR AF: 0.0150

Gnomad4 ASJ AF: 0.0602

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.245

Gnomad4 FIN AF: 0.0755

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0177 Hom.: 19

Bravo AF: 0.0330

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.87
Dann	Benign	0.41

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: rs10490422; hg19: chr2-162916413;