dbSNP rs2109069: DPP9:c.56+420C>T (chr19-4719431-G-A) – 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+420C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 168,646 control chromosomes in the GnomAD database, including 6,524 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 0.27 ( 5874 hom., cov: 33)

Exomes 𝑓: 0.26 ( 650 hom. )

Consequence

DPP9
NM_139159.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.770

Publications

101 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 (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP9	NM_139159.5 link	c.56+420C>T		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+420C>T		intron_variant	Intron 3 of 21	1	NM_139159.5	ENSP00000262960.8

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41204

AN:

151884

Hom.:

5865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.218

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.198

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.268

GnomAD4 exome

AF:

0.263

AC:

4373

AN:

16646

Hom.:

650

Cov.:

AF XY:

0.264

AC XY:

2339

AN XY:

8866

show subpopulations

African (AFR)

AF:

0.197

AC:

157

AN:

796

American (AMR)

AF:

0.239

AC:

492

AN:

2058

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

AN:

418

East Asian (EAS)

AF:

0.105

AC:

136

AN:

1298

South Asian (SAS)

AF:

0.199

AC:

230

AN:

1154

European-Finnish (FIN)

AF:

0.348

AC:

108

AN:

310

Middle Eastern (MID)

AF:

0.224

AC:

AN:

European-Non Finnish (NFE)

AF:

0.301

AC:

2917

AN:

9698

Other (OTH)

AF:

0.279

AC:

239

AN:

856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

152

303

455

606

758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

192

240

<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:

0.271

AC:

41238

AN:

152000

Hom.:

5874

Cov.:

AF XY:

0.269

AC XY:

20008

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.219

AC:

9062

AN:

41460

American (AMR)

AF:

0.249

AC:

3806

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

669

AN:

3470

East Asian (EAS)

AF:

0.133

AC:

689

AN:

5186

South Asian (SAS)

AF:

0.198

AC:

954

AN:

4826

European-Finnish (FIN)

AF:

0.349

AC:

3675

AN:

10540

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.315

AC:

21379

AN:

67930

Other (OTH)

AF:

0.267

AC:

563

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1563

3125

4688

6250

7813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

420

840

1260

1680

2100

<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:

0.295

Hom.:

25339

Bravo

AF:

0.266

Asia WGS

AF:

0.153

AC:

532

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.45

(source)

DANN

Benign

0.22

PhyloP100

-0.77

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