dbSNP rs12610495: DPP9:c.56+2191T>C (chr19-4717660-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_139159.5(DPP9):c.56+2191T>C variant causes a intron change. The variant allele was found at a frequency of 0.245 in 152,216 control chromosomes in the GnomAD database, including 4,985 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 0.25 ( 4984 hom., cov: 33)

Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

DPP9
NM_139159.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.58

Publications

75 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 Gene-Disease associations (from GenCC):

hatipoglu immunodeficiency syndrome
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

DPP9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.251169E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP9	NM_139159.5 link	c.56+2191T>C		intron_variant	Intron 3 of 21	ENST00000262960.14	NP_631898.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP9	ENST00000262960.14 link	c.56+2191T>C		intron_variant	Intron 3 of 21	1	NM_139159.5	ENSP00000262960.8

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37274

AN:

152090

Hom.:

4979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.229

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.239

GnomAD2 exomes

AF:

0.250

AC:

AN:

AF XY:

0.286

show subpopulations

Gnomad AFR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.500

Gnomad NFE exome

AF:

0.269

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

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:

0.245

AC:

37295

AN:

152208

Hom.:

4984

Cov.:

AF XY:

0.244

AC XY:

18187

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.160

AC:

6634

AN:

41528

American (AMR)

AF:

0.229

AC:

3504

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

716

AN:

3472

East Asian (EAS)

AF:

0.137

AC:

711

AN:

5180

South Asian (SAS)

AF:

0.185

AC:

891

AN:

4826

European-Finnish (FIN)

AF:

0.344

AC:

3641

AN:

10590

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.298

AC:

20265

AN:

68006

Other (OTH)

AF:

0.238

AC:

503

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1484

2968

4451

5935

7419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

386

772

1158

1544

1930

<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:

0.267

Hom.:

17953

Bravo

AF:

0.237

TwinsUK

AF:

0.297

AC:

1103

ALSPAC

AF:

0.297

AC:

1146

ExAC

AF:

0.0933

AC:

372

Asia WGS

AF:

0.139

AC:

484

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.092

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.19

MetaRNN

Benign

0.00053

PhyloP100

3.6

GERP RS

3.5

PromoterAI

-0.048

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over