2-115739765-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_020868.6(DPP10):​c.724C>A​(p.His242Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

DPP10
NM_020868.6 missense

Scores

8
9
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.811

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DPP10NM_020868.6 linkc.724C>A p.His242Asn missense_variant Exon 9 of 26 ENST00000410059.6 NP_065919.3 Q8N608-1B2RCJ8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DPP10ENST00000410059.6 linkc.724C>A p.His242Asn missense_variant Exon 9 of 26 1 NM_020868.6 ENSP00000386565.1 Q8N608-1

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152136
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000265
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:
0.0000199
AC:
5
AN:
250986
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135626
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.0000578
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:
0.00000890
AC:
13
AN:
1461182
Hom.:
0
Cov.:
30
AF XY:
0.0000110
AC XY:
8
AN XY:
726904
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.0000447
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:
0.0000331
GnomAD4 genome
AF:
0.0000722
AC:
11
AN:
152254
Hom.:
0
Cov.:
31
AF XY:
0.0000672
AC XY:
5
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.000265
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:
0.0000658
Hom.:
0
Bravo
AF:
0.000113
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.736C>A (p.H246N) alteration is located in exon 9 (coding exon 9) of the DPP10 gene. This alteration results from a C to A substitution at nucleotide position 736, causing the histidine (H) at amino acid position 246 to be replaced by an asparagine (N). 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
Uncertain
0.42
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Pathogenic
0.25
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Benign
0.18
T;.;.;.;.
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D
M_CAP
Uncertain
0.21
D
MetaRNN
Pathogenic
0.81
D;D;D;D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Uncertain
2.1
M;.;.;.;.
PrimateAI
Pathogenic
0.79
T
PROVEAN
Pathogenic
-5.4
D;D;D;D;D
REVEL
Uncertain
0.53
Sift
Uncertain
0.0030
D;D;D;D;D
Sift4G
Uncertain
0.0090
D;D;D;D;D
Polyphen
1.0
D;.;.;.;D
Vest4
0.92
MVP
0.91
MPC
0.56
ClinPred
0.88
D
GERP RS
5.1
Varity_R
0.97
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs138750698; hg19: chr2-116497341; API