19-4689623-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_139159.5(DPP9):c.1696G>A(p.Glu566Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00339 in 1,572,348 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (15 hom.)
• Consequence: DPP9 NM_139159.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.04

Genes affected

DPP9 (HGNC:18648): (dipeptidyl peptidase 9) This gene encodes a protein that is a member of the S9B family in clan SC of the serine proteases. The protein has been shown to have post-proline dipeptidyl aminopeptidase activity, cleaving Xaa-Pro dipeptides from the N-termini of proteins. Although the activity of this protein is similar to that of dipeptidyl peptidase 4 (DPP4), it does not appear to be membrane bound. In general, dipeptidyl peptidases appear to be involved in the regulation of the activity of their substrates and have been linked to a variety of diseases including type 2 diabetes, obesity and cancer. Several transcript variants of this gene have been described but not fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010352105).
• BP6: Variant 19-4689623-C-T is Benign according to our data. Variant chr19-4689623-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 717743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP9	NM_139159.5	c.1696G>A	p.Glu566Lys	missense_variant	15/22	ENST00000262960.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP9	ENST00000262960.14	c.1696G>A	p.Glu566Lys	missense_variant	15/22	1	NM_139159.5	P1

Frequencies

GnomAD3 genomes AF: 0.00212 AC: 322 AN: 152200 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000917

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000981

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00369

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00226 AC: 412 AN: 182650 Hom.: 3 AF XY: 0.00247 AC XY: 243 AN XY: 98380

Gnomad AFR exome AF: 0.000786

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.00227

Gnomad EAS exome AF: 0.0000750

Gnomad SAS exome AF: 0.000578

Gnomad FIN exome AF: 0.000249

Gnomad NFE exome AF: 0.00383

Gnomad OTH exome AF: 0.00376

GnomAD4 exome AF: 0.00352 AC: 5002 AN: 1420030 Hom.: 15 Cov.: 32 AF XY: 0.00345 AC XY: 2426 AN XY: 702756

Gnomad4 AFR exome AF: 0.000707

Gnomad4 AMR exome AF: 0.00215

Gnomad4 ASJ exome AF: 0.00126

Gnomad4 EAS exome AF: 0.0000537

Gnomad4 SAS exome AF: 0.000583

Gnomad4 FIN exome AF: 0.000363

Gnomad4 NFE exome AF: 0.00425

Gnomad4 OTH exome AF: 0.00221

GnomAD4 genome AF: 0.00211 AC: 321 AN: 152318 Hom.: 1 Cov.: 32 AF XY: 0.00187 AC XY: 139 AN XY: 74482

Gnomad4 AFR AF: 0.000914

Gnomad4 AMR AF: 0.000980

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00369

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00377 Hom.: 6

Bravo AF: 0.00222

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.000956 AC: 4

ESP6500EA AF: 0.00286 AC: 24

ExAC AF: 0.00207 AC: 245

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	DPP9: BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.38
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Benign	-0.039
Eigen_PC	Benign	0.051
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D;D
MetaRNN	Benign	0.010	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.60	T
Sift4G	Benign	0.31	T;T;T
Vest4		0.60
MVP		0.20
MPC		0.80
ClinPred		0.024	T
GERP RS		4.0
Varity_R		0.21
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200229921; hg19: chr19-4689635; COSMIC: COSV104368844; COSMIC: COSV104368844;