2-115768323-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_020868.6(DPP10):c.1140C>T(p.Asp380=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000964 in 1,613,560 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00057 (6 hom.)
• Consequence: DPP10 NM_020868.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.244

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 2-115768323-C-T is Benign according to our data. Variant chr2-115768323-C-T is described in ClinVar as [Benign]. Clinvar id is 780833.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.244 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP10	NM_020868.6	c.1140C>T	p.Asp380=	synonymous_variant	13/26	ENST00000410059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP10	ENST00000410059.6	c.1140C>T	p.Asp380=	synonymous_variant	13/26	1	NM_020868.6	A1
DPP10	ENST00000393147.6	c.1152C>T	p.Asp384=	synonymous_variant	13/26	1		P3
DPP10	ENST00000310323.12	c.1119C>T	p.Asp373=	synonymous_variant	13/26	1
DPP10	ENST00000409163.5	c.990C>T	p.Asp330=	synonymous_variant	14/27	2

Frequencies

GnomAD3 genomes AF: 0.00473 AC: 720 AN: 152094 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00354

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00129 AC: 323 AN: 250968 Hom.: 3 AF XY: 0.000981 AC XY: 133 AN XY: 135620

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.000980

GnomAD4 exome AF: 0.000567 AC: 828 AN: 1461348 Hom.: 6 Cov.: 29 AF XY: 0.000531 AC XY: 386 AN XY: 726974

Gnomad4 AFR exome AF: 0.0154

Gnomad4 AMR exome AF: 0.00166

Gnomad4 ASJ exome AF: 0.000804

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000105

Gnomad4 OTH exome AF: 0.00144

GnomAD4 genome AF: 0.00478 AC: 727 AN: 152212 Hom.: 7 Cov.: 32 AF XY: 0.00495 AC XY: 368 AN XY: 74386

Gnomad4 AFR AF: 0.0155

Gnomad4 AMR AF: 0.00354

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00213 Hom.: 0

Bravo AF: 0.00571

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
Cadd	Benign	12
Dann	Benign	0.63

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

LitVar

Other links and lift over

dbSNP: rs34741590; hg19: chr2-116525899; COSMIC: COSV59722455;