2-115525921-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_020868.6(DPP10):c.390T>C(p.His130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,609,716 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (7 hom.)
• Consequence: DPP10 NM_020868.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.328

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 2-115525921-T-C is Benign according to our data. Variant chr2-115525921-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 715475.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.328 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP10	NM_020868.6	c.390T>C	p.His130=	synonymous_variant	5/26	ENST00000410059.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP10	ENST00000410059.6	c.390T>C	p.His130=	synonymous_variant	5/26	1	NM_020868.6	A1

Frequencies

GnomAD3 genomes AF: 0.00128 AC: 194 AN: 152046 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00229

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.00117 AC: 289 AN: 247426 Hom.: 0 AF XY: 0.00126 AC XY: 169 AN XY: 133790

Gnomad AFR exome AF: 0.000435

Gnomad AMR exome AF: 0.000473

Gnomad ASJ exome AF: 0.000702

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000333

Gnomad FIN exome AF: 0.000764

Gnomad NFE exome AF: 0.00209

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.00193 AC: 2814 AN: 1457552 Hom.: 7 Cov.: 30 AF XY: 0.00187 AC XY: 1357 AN XY: 725076

Gnomad4 AFR exome AF: 0.000300

Gnomad4 AMR exome AF: 0.000406

Gnomad4 ASJ exome AF: 0.000653

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000817

Gnomad4 FIN exome AF: 0.00103

Gnomad4 NFE exome AF: 0.00237

Gnomad4 OTH exome AF: 0.00120

GnomAD4 genome AF: 0.00127 AC: 194 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.00126 AC XY: 94 AN XY: 74396

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00230

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00187 Hom.: 0

Bravo AF: 0.00124

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 17, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	7.1
Dann	Benign	0.67

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: rs138259404; hg19: chr2-116283497;