2-162053713-G-C

Variant names:

• chr2-162053713-G-C
• rs6741949
• NM_001935.4:c.95-6212C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001935.4(DPP4):​c.95-6212C>G 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 152,186 control chromosomes in the GnomAD database, including 9,435 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 0.33 (9435 hom., cov: 33)
• Consequence: DPP4 NM_001935.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175
• Publications: 29 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP4	NM_001935.4	c.95-6212C>G		intron_variant	Intron 2 of 25	ENST00000360534.8	NP_001926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP4	ENST00000360534.8	c.95-6212C>G		intron_variant	Intron 2 of 25	1	NM_001935.4	ENSP00000353731.3

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50198 AN: 152068 Hom.: 9420 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.346

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

GnomAD4 genome AF: 0.330 AC: 50231 AN: 152186 Hom.: 9435 Cov.: 33 AF XY: 0.328 AC XY: 24416 AN XY: 74398

African (AFR) AF: 0.161 AC: 6689 AN: 41542

American (AMR) AF: 0.418 AC: 6390 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1164 AN: 3468

East Asian (EAS) AF: 0.100 AC: 520 AN: 5180

South Asian (SAS) AF: 0.382 AC: 1843 AN: 4824

European-Finnish (FIN) AF: 0.364 AC: 3842 AN: 10566

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28693 AN: 67992

Other (OTH) AF: 0.342 AC: 721 AN: 2110

Alfa AF: 0.263 Hom.: 776

Bravo AF: 0.325

Asia WGS AF: 0.237 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.0
DANN	Benign	0.43
PhyloP100		-0.17
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: rs6741949; hg19: chr2-162910223;