rs949577

Positions:

• chr2-114985970-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020868.6(DPP10):​c.61-323269A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,182 control chromosomes in the GnomAD database, including 3,595 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3595 hom., cov: 33)
• Consequence: DPP10 NM_020868.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DPP10	NM_020868.6	c.61-323269A>G		intron_variant		ENST00000410059.6	NP_065919.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DPP10	ENST00000410059.6	c.61-323269A>G		intron_variant		1	NM_020868.6	ENSP00000386565.1
DPP10	ENST00000409163.5	c.-90-323269A>G		intron_variant		2		ENSP00000387038.1
DPP10	ENST00000436732.5	c.-162-64178A>G		intron_variant		4		ENSP00000391092.1
DPP10	ENST00000461250.5	n.654+278796A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31737 AN: 152062 Hom.: 3590 Cov.: 33

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.368

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.243

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.209 AC: 31753 AN: 152182 Hom.: 3595 Cov.: 33 AF XY: 0.216 AC XY: 16084 AN XY: 74390

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.245

Alfa AF: 0.229 Hom.: 2358

Bravo AF: 0.197

Asia WGS AF: 0.337 AC: 1171 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.74
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs949577; hg19: chr2-115743547;