rs11243354

Positions:

• chr7-154587524-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000496611.2(DPP6):​c.*350T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,007,696 control chromosomes in the GnomAD database, including 23,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6990 hom., cov: 32)
  • Exomes 𝑓: 0.18 (16350 hom.)
• Consequence: DPP6 ENST00000496611.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0380

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-154587524-T-C is Benign according to our data. Variant chr7-154587524-T-C is described in ClinVar as [Benign]. Clinvar id is 1237202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4	c.627+20608T>C		intron_variant		ENST00000377770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8	c.627+20608T>C		intron_variant		1	NM_130797.4

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40351 AN: 151670 Hom.: 6969 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0853

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.184 AC: 157485 AN: 855908 Hom.: 16350 Cov.: 11 AF XY: 0.183 AC XY: 78904 AN XY: 431360

Gnomad4 AFR exome AF: 0.515

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.0689

Gnomad4 SAS exome AF: 0.166

Gnomad4 FIN exome AF: 0.156

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.266 AC: 40423 AN: 151788 Hom.: 6990 Cov.: 32 AF XY: 0.262 AC XY: 19434 AN XY: 74196

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0851

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.231

Alfa AF: 0.207 Hom.: 792

Bravo AF: 0.284

Asia WGS AF: 0.147 AC: 510 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 11, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.72
DANN	Benign	0.46

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: rs11243354; hg19: chr7-154379234;