Variant 2-115343844-G-C 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.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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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

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:

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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=0.07830703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP10	NM_020868.6 linkuse as main transcript	c.203G>C	p.Arg68Thr	missense_variant	3/26	ENST00000410059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP10	ENST00000410059.6 linkuse as main transcript	c.203G>C	p.Arg68Thr	missense_variant	3/26	1	NM_020868.6	A1	Q8N608-1

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

GnomAD3 exomes

AF:

0.0000561

AC:

AN:

249620

Hom.:

AF XY:

0.0000296

AC XY:

AN XY:

134922

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 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:

0.0000137

AC:

AN:

1459478

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725966

show subpopulations

Gnomad4 AFR exome

AF:

0.000509

Gnomad4 AMR exome

AF:

0.00

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:

0.0000166

GnomAD4 genome

AF:

0.000224

AC:

AN:

151946

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.000797

Gnomad4 AMR

AF:

0.0000655

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:

0.000142

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

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

Feb 13, 2023

The c.215G>C (p.R72T) alteration is located in exon 3 (coding exon 3) of the DPP10 gene. This alteration results from a G to C substitution at nucleotide position 215, causing the arginine (R) at amino acid position 72 to be replaced by a threonine (T). 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

0.13

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Uncertain

0.13

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.084

T;T;.;.;.;.;.

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.89

D;D;D;D;D;D;D

M_CAP

Benign

0.078

MetaRNN

Benign

0.078

T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.073

MutationTaster

Benign

0.94

D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.5

D;N;N;D;N;N;D

REVEL

Benign

0.29

Sift

Uncertain

0.013

D;T;D;T;T;T;D

Sift4G

Benign

0.068

T;T;T;T;T;T;T

Polyphen

0.0040, 0.0060

.;B;.;.;.;B;.

Vest4

0.69, 0.74, 0.68

MVP

0.90

MPC

0.24

ClinPred

0.055

GERP RS

3.1

Varity_R

0.15

gMVP

0.53

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

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