rs2192271

chr7-153852211-C-T

Variant summary

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

The NM_001364497.2(DPP6):c.60+103203C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,172 control chromosomes in the GnomAD database, including 2,693 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 0.18 (2693 hom., cov: 32)
• Consequence: DPP6 NM_001364497.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

Genes affected

DPP6 (HGNC:3010): (dipeptidyl peptidase like 6) This gene encodes a single-pass type II membrane protein that is a member of the peptidase S9B family of 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. Variations in this gene may be associated with susceptibility to amyotrophic lateral sclerosis and with idiopathic ventricular fibrillation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

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 = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_001364497.2	c.60+103203C>T		intron_variant
DPP6	NM_001364498.2	c.60+103203C>T		intron_variant
DPP6	NM_001364499.2	c.60+103203C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000706130.1	c.60+103203C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28109 AN: 152054 Hom.: 2692 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.185 AC: 28130 AN: 152172 Hom.: 2693 Cov.: 32 AF XY: 0.181 AC XY: 13444 AN XY: 74404

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.199

Alfa AF: 0.211 Hom.: 5867

Bravo AF: 0.186

Asia WGS AF: 0.193 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.7
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2192271; hg19: chr7-153549296;