2-115115219-C-T

Variant names:

• chr2-115115219-C-T
• rs4277531
• NM_020868.6:c.61-194020C>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.112-194020C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,858 control chromosomes in the GnomAD database, including 15,919 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 0.45 (15919 hom., cov: 31)
• Consequence: DPP10 NM_001321905.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 4 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]

LOC105373574 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP10	NM_020868.6	MANE Select	c.61-194020C>T		intron	N/A	NP_065919.3
	DPP10	NM_001321905.3		c.112-194020C>T		intron	N/A	NP_001308834.2
	DPP10	NM_001178037.3		c.48+50414C>T		intron	N/A	NP_001171508.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP10	ENST00000410059.6	TSL:1 MANE Select	c.61-194020C>T		intron	N/A	ENSP00000386565.1
	DPP10	ENST00000409163.5	TSL:2	c.-90-194020C>T		intron	N/A	ENSP00000387038.1
	DPP10	ENST00000393146.6	TSL:5	c.48+50414C>T		intron	N/A	ENSP00000376854.2

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68910 AN: 151740 Hom.: 15901 Cov.: 31

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.454 AC: 68987 AN: 151858 Hom.: 15919 Cov.: 31 AF XY: 0.457 AC XY: 33925 AN XY: 74226

African (AFR) AF: 0.488 AC: 20205 AN: 41404

American (AMR) AF: 0.495 AC: 7561 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1702 AN: 3466

East Asian (EAS) AF: 0.667 AC: 3399 AN: 5098

South Asian (SAS) AF: 0.428 AC: 2059 AN: 4812

European-Finnish (FIN) AF: 0.453 AC: 4788 AN: 10566

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27803 AN: 67930

Other (OTH) AF: 0.438 AC: 922 AN: 2104

Alfa AF: 0.422 Hom.: 39278

Bravo AF: 0.463

Asia WGS AF: 0.549 AC: 1911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.27
DANN	Benign	0.57
PhyloP100		-1.2
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: rs4277531; hg19: chr2-115872796; COSMIC: COSV67714047;