2-115768364-G-C

Variant summary

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

The NM_020868.6(DPP10):c.1181G>C(p.Gly394Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DPP10 NM_020868.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP10	NM_020868.6	c.1181G>C	p.Gly394Ala	missense_variant	13/26	ENST00000410059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP10	ENST00000410059.6	c.1181G>C	p.Gly394Ala	missense_variant	13/26	1	NM_020868.6	A1
DPP10	ENST00000393147.6	c.1193G>C	p.Gly398Ala	missense_variant	13/26	1		P3
DPP10	ENST00000310323.12	c.1160G>C	p.Gly387Ala	missense_variant	13/26	1
DPP10	ENST00000409163.5	c.1031G>C	p.Gly344Ala	missense_variant	14/27	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

Aug 13, 2021

The c.1193G>C (p.G398A) alteration is located in exon 13 (coding exon 13) of the DPP10 gene. This alteration results from a G to C substitution at nucleotide position 1193, causing the glycine (G) at amino acid position 398 to be replaced by an alanine (A). 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	0.23
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;.;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.64	D;D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.95	L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-4.0	D;D;D;D
REVEL	Uncertain	0.32
Sift	Benign	0.085	T;T;T;T
Sift4G	Benign	0.22	T;T;T;T
Polyphen		0.74	P;.;.;P
Vest4		0.77
MutPred		0.46		Loss of sheet (P = 0.0315);.;.;.;
MVP		0.42
MPC		0.18
ClinPred		0.97	D
GERP RS		5.3
Varity_R		0.62
gMVP		0.62

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-116525940;