2-162029379-A-G

Variant names:

• chr2-162029379-A-G
• rs4664443
• NM_001935.4:c.887+4162T>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.887+4162T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,130 control chromosomes in the GnomAD database, including 21,185 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 0.51 (21185 hom., cov: 33)
• Consequence: DPP4 NM_001935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 13 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.932 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP4	NM_001935.4	c.887+4162T>C		intron_variant	Intron 10 of 25	ENST00000360534.8	NP_001926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP4	ENST00000360534.8	c.887+4162T>C		intron_variant	Intron 10 of 25	1	NM_001935.4	ENSP00000353731.3

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76783 AN: 152012 Hom.: 21148 Cov.: 33

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.505 AC: 76871 AN: 152130 Hom.: 21185 Cov.: 33 AF XY: 0.512 AC XY: 38038 AN XY: 74340

African (AFR) AF: 0.668 AC: 27754 AN: 41528

American (AMR) AF: 0.417 AC: 6377 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1879 AN: 3470

East Asian (EAS) AF: 0.954 AC: 4937 AN: 5174

South Asian (SAS) AF: 0.563 AC: 2716 AN: 4826

European-Finnish (FIN) AF: 0.491 AC: 5192 AN: 10572

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.391 AC: 26541 AN: 67962

Other (OTH) AF: 0.461 AC: 973 AN: 2112

Alfa AF: 0.473 Hom.: 3428

Bravo AF: 0.507

Asia WGS AF: 0.740 AC: 2571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.2
DANN	Benign	0.52
PhyloP100		0.36
Mutation Taster		=100/0	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: rs4664443; hg19: chr2-162885889;