chr2-115768339-A-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_020868.6(DPP10):c.1156A>T(p.Met386Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000868 in 1,613,610 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 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
DPP10
NM_020868.6 missense
NM_020868.6 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 3.88
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 Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.06250295).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DPP10 | NM_020868.6 | c.1156A>T | p.Met386Leu | missense_variant | 13/26 | ENST00000410059.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DPP10 | ENST00000410059.6 | c.1156A>T | p.Met386Leu | missense_variant | 13/26 | 1 | NM_020868.6 | A1 | |
DPP10 | ENST00000393147.6 | c.1168A>T | p.Met390Leu | missense_variant | 13/26 | 1 | P3 | ||
DPP10 | ENST00000310323.12 | c.1135A>T | p.Met379Leu | missense_variant | 13/26 | 1 | |||
DPP10 | ENST00000409163.5 | c.1006A>T | p.Met336Leu | missense_variant | 14/27 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
6
AN:
152170
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251138Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135708
GnomAD3 exomes
AF:
AC:
3
AN:
251138
Hom.:
AF XY:
AC XY:
2
AN XY:
135708
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461440Hom.: 0 Cov.: 29 AF XY: 0.00000688 AC XY: 5AN XY: 727016
GnomAD4 exome
AF:
AC:
8
AN:
1461440
Hom.:
Cov.:
29
AF XY:
AC XY:
5
AN XY:
727016
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74330
GnomAD4 genome
?
AF:
AC:
6
AN:
152170
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
74330
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
1
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 12, 2024 | The c.1168A>T (p.M390L) alteration is located in exon 13 (coding exon 13) of the DPP10 gene. This alteration results from a A to T substitution at nucleotide position 1168, causing the methionine (M) at amino acid position 390 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
B;.;.;B
Vest4
MutPred
Loss of ubiquitination at K391 (P = 0.0853);.;.;.;
MVP
MPC
0.15
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at