chr2-114841436-G-T

Variant names:

• chr2-114841436-G-T
• rs10496476
• NM_020868.6:c.60+398598G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321905.3(DPP10):​c.111+134262G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 152,092 control chromosomes in the GnomAD database, including 4,252 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 0.23 (4252 hom., cov: 32)
• Consequence: DPP10 NM_001321905.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321905.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP10	NM_020868.6	MANE Select	c.60+398598G>T		intron	N/A	NP_065919.3
	DPP10	NM_001321905.3		c.111+134262G>T		intron	N/A	NP_001308834.2
	DPP10	NM_001321907.3		c.60+398598G>T		intron	N/A	NP_001308836.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP10	ENST00000410059.6	TSL:1 MANE Select	c.60+398598G>T		intron	N/A	ENSP00000386565.1
	DPP10	ENST00000409163.5	TSL:2	c.-91+378010G>T		intron	N/A	ENSP00000387038.1
	DPP10	ENST00000436732.5	TSL:4	c.-162-208712G>T		intron	N/A	ENSP00000391092.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34645 AN: 151974 Hom.: 4256 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.228 AC: 34640 AN: 152092 Hom.: 4252 Cov.: 32 AF XY: 0.228 AC XY: 16975 AN XY: 74342

African (AFR) AF: 0.134 AC: 5581 AN: 41526

American (AMR) AF: 0.234 AC: 3574 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1160 AN: 3468

East Asian (EAS) AF: 0.373 AC: 1925 AN: 5166

South Asian (SAS) AF: 0.224 AC: 1080 AN: 4828

European-Finnish (FIN) AF: 0.283 AC: 2992 AN: 10564

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.257 AC: 17477 AN: 67962

Other (OTH) AF: 0.251 AC: 529 AN: 2108

Alfa AF: 0.244 Hom.: 8794

Bravo AF: 0.223

Asia WGS AF: 0.243 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.52
DANN	Benign	0.35
PhyloP100		-0.046
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10496476; hg19: chr2-115599013;