2-162009238-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001935.4(DPP4):c.1887+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00962 in 1,613,638 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (2 hom., cov: 32)
  • Exomes 𝑓: 0.010 (107 hom.)
• Consequence: DPP4 NM_001935.4 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0001687
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.913

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 2-162009238-C-T is Benign according to our data. Variant chr2-162009238-C-T is described in ClinVar as [Benign]. Clinvar id is 710726.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP4	NM_001935.4	c.1887+3G>A		splice_donor_region_variant, intron_variant		ENST00000360534.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP4	ENST00000360534.8	c.1887+3G>A		splice_donor_region_variant, intron_variant		1	NM_001935.4	P3

Frequencies

GnomAD3 genomes AF: 0.00586 AC: 891 AN: 152172 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00452 AC: 1136 AN: 251194 Hom.: 4 AF XY: 0.00430 AC XY: 584 AN XY: 135756

Gnomad AFR exome AF: 0.00135

Gnomad AMR exome AF: 0.00266

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00208

Gnomad NFE exome AF: 0.00833

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.0100 AC: 14629 AN: 1461348 Hom.: 107 Cov.: 30 AF XY: 0.00956 AC XY: 6952 AN XY: 727004

Gnomad4 AFR exome AF: 0.00179

Gnomad4 AMR exome AF: 0.00260

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00221

Gnomad4 NFE exome AF: 0.0124

Gnomad4 OTH exome AF: 0.00939

GnomAD4 genome AF: 0.00584 AC: 890 AN: 152290 Hom.: 2 Cov.: 32 AF XY: 0.00559 AC XY: 416 AN XY: 74462

Gnomad4 AFR AF: 0.00221

Gnomad4 AMR AF: 0.00523

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00715 Hom.: 2

Bravo AF: 0.00578

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00911

EpiControl AF: 0.00889

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
Cadd	Benign	18
Dann	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00017
dbscSNV1_RF	Benign	0.012
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: rs115450134; hg19: chr2-162865748;