2-162008558-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001935.4(DPP4):c.1987+4T>C 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 0.00267 in 1,612,816 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (90 hom.)
• Consequence: DPP4 NM_001935.4 splice_donor_region, intron
• Scores: Splicing: ADA: 0.00007068
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.570

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 2-162008558-A-G is Benign according to our data. Variant chr2-162008558-A-G is described in ClinVar as [Benign]. Clinvar id is 715707.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP4	NM_001935.4	c.1987+4T>C		splice_donor_region_variant, intron_variant		ENST00000360534.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP4	ENST00000360534.8	c.1987+4T>C		splice_donor_region_variant, intron_variant		1	NM_001935.4	P3

Frequencies

GnomAD3 genomes AF: 0.00263 AC: 399 AN: 151984 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000750

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00958

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00521 AC: 1306 AN: 250884 Hom.: 12 AF XY: 0.00425 AC XY: 576 AN XY: 135580

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.0183

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.0256

Gnomad SAS exome AF: 0.00206

Gnomad FIN exome AF: 0.000324

Gnomad NFE exome AF: 0.000697

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00267 AC: 3907 AN: 1460714 Hom.: 90 Cov.: 30 AF XY: 0.00259 AC XY: 1880 AN XY: 726724

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.0172

Gnomad4 ASJ exome AF: 0.000881

Gnomad4 EAS exome AF: 0.0563

Gnomad4 SAS exome AF: 0.00241

Gnomad4 FIN exome AF: 0.000206

Gnomad4 NFE exome AF: 0.000469

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.00263 AC: 400 AN: 152102 Hom.: 4 Cov.: 32 AF XY: 0.00288 AC XY: 214 AN XY: 74346

Gnomad4 AFR AF: 0.000747

Gnomad4 AMR AF: 0.00963

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.0292

Gnomad4 SAS AF: 0.00291

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00206 Hom.: 2

Bravo AF: 0.00393

Asia WGS AF: 0.0180 AC: 61 AN: 3478

EpiCase AF: 0.000437

EpiControl AF: 0.000356

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	-0.75
Cadd	Benign	6.8
Dann	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000071
dbscSNV1_RF	Benign	0.082
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: rs2268891; hg19: chr2-162865068;