rs149933026

Variant names:

• chr2-115727816-A-C
• NM_020868.6:c.577A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-115727816-A-C
• chr2-115727816-A-G

Variant summary

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

The NM_020868.6(DPP10):​c.577A>C​(p.Ile193Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000698 in 1,431,910 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I193V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: DPP10 NM_020868.6 missense, splice_region
• Scores: Splicing: ADA: 0.7874
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.40

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 rank	MANE	Protein	UniProt
DPP10	NM_020868.6	c.577A>C	p.Ile193Leu	missense_variant, splice_region_variant	Exon 8 of 26	ENST00000410059.6	NP_065919.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP10	ENST00000410059.6	c.577A>C	p.Ile193Leu	missense_variant, splice_region_variant	Exon 8 of 26	1	NM_020868.6	ENSP00000386565.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1431910 Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1 AN XY: 711064

Gnomad4 AFR exome AF: 0.00

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: 0.0000169

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T;.;.;.;.
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.68	D;D;D;D;D
MetaSVM	Pathogenic	0.88	D
MutationAssessor	Benign	1.6	L;.;.;.;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.4	N;N;N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.010	D;D;D;D;D
Sift4G	Uncertain	0.048	D;D;T;D;D
Polyphen		0.89	P;.;.;.;P
Vest4		0.61
MutPred		0.68		Loss of stability (P = 0.1954);.;.;.;.;
MVP		0.70
MPC		0.16
ClinPred		0.89	D
GERP RS		5.5
Varity_R		0.70
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.79
dbscSNV1_RF	Benign	0.54
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-116485392;