2-115762594-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020868.6(DPP10):c.1097C>T(p.Thr366Met) variant causes a missense change. The variant allele was found at a frequency of 0.000252 in 1,613,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (0 hom.)
• Consequence: DPP10 NM_020868.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81

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]

ACMG classification

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=0.13122275).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP10	NM_020868.6	c.1097C>T	p.Thr366Met	missense_variant	12/26	ENST00000410059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP10	ENST00000410059.6	c.1097C>T	p.Thr366Met	missense_variant	12/26	1	NM_020868.6	A1
DPP10	ENST00000393147.6	c.1109C>T	p.Thr370Met	missense_variant	12/26	1		P3
DPP10	ENST00000310323.12	c.1076C>T	p.Thr359Met	missense_variant	12/26	1
DPP10	ENST00000409163.5	c.947C>T	p.Thr316Met	missense_variant	13/27	2

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152104 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000394

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: 0.000309

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000155 AC: 39 AN: 250910 Hom.: 0 AF XY: 0.000140 AC XY: 19 AN XY: 135636

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000317

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000257 AC: 376 AN: 1461282 Hom.: 0 Cov.: 31 AF XY: 0.000259 AC XY: 188 AN XY: 726964

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000377

Gnomad4 NFE exome AF: 0.000308

Gnomad4 OTH exome AF: 0.000331

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74418

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000459

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.000266 Hom.: 0

Bravo AF: 0.000314

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000148 AC: 18

EpiCase AF: 0.000218

EpiControl AF: 0.000296

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2022

The c.1109C>T (p.T370M) alteration is located in exon 12 (coding exon 12) of the DPP10 gene. This alteration results from a C to T substitution at nucleotide position 1109, causing the threonine (T) at amino acid position 370 to be replaced by a methionine (M). 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	0.072
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.45
Cadd	Uncertain	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.066	T;.;.;.
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;.;.;.
MutationTaster	Benign	0.79	N;N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.0	N;N;N;N
REVEL	Benign	0.084
Sift	Uncertain	0.017	D;D;D;D
Sift4G	Uncertain	0.055	T;T;T;T
Polyphen		0.82	P;.;.;P
Vest4		0.22
MVP		0.12
MPC		0.19
ClinPred		0.10	T
GERP RS		4.0
Varity_R		0.16
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.20		Position offset: 16

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201296031; hg19: chr2-116520170; COSMIC: COSV59668659;