Genetic Variant DPP9:p.Asp612Asn (chr19-4688808-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_139159.5(DPP9):c.1834G>A(p.Asp612Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000303 in 1,484,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

DPP9
NM_139159.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00

Publications

0 publications found

Variant links:

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]

DPP9 links:

DPP9-AS1 (HGNC:50706): (DPP9 antisense RNA 1)

DPP9-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.076058984).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139159.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPP9	NM_139159.5	MANE Select	c.1834G>A	p.Asp612Asn	missense	Exon 16 of 22	NP_631898.3
DPP9	NM_001384611.1		c.1834G>A	p.Asp612Asn	missense	Exon 15 of 21	NP_001371540.1	Q86TI2-2
DPP9	NM_001384612.1		c.1834G>A	p.Asp612Asn	missense	Exon 17 of 23	NP_001371541.1	Q86TI2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPP9	ENST00000262960.14	TSL:1 MANE Select	c.1834G>A	p.Asp612Asn	missense	Exon 16 of 22	ENSP00000262960.8	Q86TI2-2
DPP9	ENST00000600621.6	TSL:4	c.1834G>A	p.Asp612Asn	missense	Exon 16 of 22	ENSP00000472549.2	Q86TI2-2
DPP9	ENST00000601130.6	TSL:4	c.1834G>A	p.Asp612Asn	missense	Exon 17 of 23	ENSP00000471629.2	Q86TI2-2

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000555

AC:

AN:

144046

AF XY:

0.0000369

show subpopulations

Gnomad AFR exome

AF:

0.000670

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000271

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000173

AC:

AN:

1331812

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

655252

show subpopulations

African (AFR)

AF:

0.000498

AC:

AN:

26108

American (AMR)

AF:

0.00

AC:

AN:

19732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21744

East Asian (EAS)

AF:

0.0000318

AC:

AN:

31432

South Asian (SAS)

AF:

0.00

AC:

AN:

66618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49292

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5368

European-Non Finnish (NFE)

AF:

0.00000852

AC:

AN:

1056646

Other (OTH)

AF:

0.00

AC:

AN:

54872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000144

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.557

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000134

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.000965

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000911

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.096

Eigen

Benign

-0.15

Eigen_PC

Benign

0.022

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0067

MetaRNN

Benign

0.076

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

5.0

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.3

REVEL

Benign

0.040

Sift

Benign

0.23

Sift4G

Benign

0.35

Vest4

0.49

MVP

0.36

MPC

0.37

ClinPred

0.052

GERP RS

4.9

PromoterAI

0.038

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.28

gMVP

0.28

Mutation Taster

=69/31

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over