Genetic Variant DPP10:p.Arg68Thr (chr2-115343844-G-C) – 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_020868.6(DPP10):c.203G>C(p.Arg68Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,611,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R68S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

DPP10
NM_020868.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.91

Publications

1 publications found

Variant links:

Genes affected

DPP10 (HGNC:20823): (dipeptidyl peptidase like 10) This gene encodes a single-pass type II membrane protein that is a member of the S9B family in clan SC of the serine proteases. This protein has no detectable protease activity, most likely due to the absence of the conserved serine residue normally present in the catalytic domain of serine proteases. However, it does bind specific voltage-gated potassium channels and alters their expression and biophysical properties. Mutations in this gene have been associated with asthma. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

DPP10 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=0.07830703).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020868.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPP10	NM_020868.6	MANE Select	c.203G>C	p.Arg68Thr	missense	Exon 3 of 26	NP_065919.3
DPP10	NM_001321905.3		c.254G>C	p.Arg85Thr	missense	Exon 4 of 27	NP_001308834.2
DPP10	NM_001178034.1		c.215G>C	p.Arg72Thr	missense	Exon 3 of 26	NP_001171505.1	Q8N608

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPP10	ENST00000410059.6	TSL:1 MANE Select	c.203G>C	p.Arg68Thr	missense	Exon 3 of 26	ENSP00000386565.1	Q8N608-1
DPP10	ENST00000393147.6	TSL:1	c.215G>C	p.Arg72Thr	missense	Exon 3 of 26	ENSP00000376855.2	Q8N608-3
DPP10	ENST00000310323.12	TSL:1	c.182G>C	p.Arg61Thr	missense	Exon 3 of 26	ENSP00000309066.8	Q8N608-2

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000561

AC:

AN:

249620

AF XY:

0.0000296

show subpopulations

Gnomad AFR exome

AF:

0.000866

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1459478

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725966

show subpopulations

African (AFR)

AF:

0.000509

AC:

AN:

33392

American (AMR)

AF:

0.00

AC:

AN:

44508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39564

South Asian (SAS)

AF:

0.00

AC:

AN:

85724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110822

Other (OTH)

AF:

0.0000166

AC:

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.000224

AC:

AN:

151946

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74174

show subpopulations

African (AFR)

AF:

0.000797

AC:

AN:

41392

American (AMR)

AF:

0.0000655

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5120

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.000142

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

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

0.13

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Uncertain

0.13

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.084

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.078

MetaRNN

Benign

0.078

MetaSVM

Uncertain

-0.073

MutationAssessor

Benign

0.98

PhyloP100

1.9

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.29

Sift

Uncertain

0.013

Sift4G

Benign

0.068

Polyphen

0.0040

Vest4

0.69

MVP

0.90

MPC

0.24

ClinPred

0.055

GERP RS

3.1

Varity_R

0.15

gMVP

0.53

Mutation Taster

=72/28

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