Variant 2-115727816-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020868.6(DPP10):c.577A>G(p.Ile193Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000202 in 1,584,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

DPP10
NM_020868.6 missense, splice_region

Scores

Splicing: ADA: 0.001502

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.40

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:

DPP10 (HGNC:):

DPP10 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19873244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP10	NM_020868.6 linkuse as main transcript	c.577A>G	p.Ile193Val	missense_variant, splice_region_variant	8/26	ENST00000410059.6	NP_065919.3	Q8N608-1B2RCJ8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP10	ENST00000410059.6 linkuse as main transcript	c.577A>G	p.Ile193Val	missense_variant, splice_region_variant	8/26	1	NM_020868.6	ENSP00000386565.1		Q8N608-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000314

AC:

AN:

223006

Hom.:

AF XY:

0.00000826

AC XY:

AN XY:

121112

show subpopulations

Gnomad AFR exome

AF:

0.000415

Gnomad AMR exome

AF:

0.0000374

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000768

AC:

AN:

1431910

Hom.:

Cov.:

AF XY:

0.00000422

AC XY:

AN XY:

711064

show subpopulations

Gnomad4 AFR exome

AF:

0.000316

Gnomad4 AMR exome

AF:

0.0000269

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000138

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.000507

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000292

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.000923

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2024

The c.589A>G (p.I197V) alteration is located in exon 8 (coding exon 8) of the DPP10 gene. This alteration results from a A to G substitution at nucleotide position 589, causing the isoleucine (I) at amino acid position 197 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.090

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

T;.;.;.;.

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

D;D;D;D;D

M_CAP

Benign

0.049

MetaRNN

Benign

0.20

T;T;T;T;T

MetaSVM

Uncertain

0.60

MutationAssessor

Benign

0.24

N;.;.;.;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.29

N;N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.19

T;T;T;T;T

Sift4G

Benign

0.41

T;T;T;T;T

Polyphen

0.11

B;.;.;.;B

Vest4

0.22

MVP

0.43

MPC

0.13

ClinPred

0.092

GERP RS

5.5

Varity_R

0.20

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0015

dbscSNV1_RF

Benign

0.024

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over