7-154052986-CGCG-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_130797.4(DPP6):c.185_187del(p.Gly62del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 146,920 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.000061 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DPP6 NM_130797.4 inframe_deletion
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: -0.431

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 Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 7-154052986-CGCG-C is Benign according to our data. Variant chr7-154052986-CGCG-C is described in ClinVar as [Likely_benign]. Clinvar id is 1299926.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr7-154052986-CGCG-C is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4	c.185_187del	p.Gly62del	inframe_deletion	1/26	ENST00000377770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8	c.185_187del	p.Gly62del	inframe_deletion	1/26	1	NM_130797.4
DPP6	ENST00000406326.5	c.185_187del	p.Gly62del	inframe_deletion	1/6	1
DPP6	ENST00000404039.5	c.51+165271_51+165273del		intron_variant		1
DPP6	ENST00000706130.1	c.60+303997_60+303999del		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0000613 AC: 9 AN: 146824 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000984

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000302

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00162 AC: 5 AN: 3080 Hom.: 0 AF XY: 0.00177 AC XY: 3 AN XY: 1692

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00673

Gnomad NFE exome AF: 0.000432

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000428 AC: 394 AN: 921448 Hom.: 0 AF XY: 0.000498 AC XY: 215 AN XY: 431814

Gnomad4 AFR exome AF: 0.000553

Gnomad4 AMR exome AF: 0.00346

Gnomad4 ASJ exome AF: 0.00182

Gnomad4 EAS exome AF: 0.00226

Gnomad4 SAS exome AF: 0.000222

Gnomad4 FIN exome AF: 0.00268

Gnomad4 NFE exome AF: 0.000322

Gnomad4 OTH exome AF: 0.000940

GnomAD4 genome AF: 0.0000613 AC: 9 AN: 146920 Hom.: 0 Cov.: 31 AF XY: 0.0000419 AC XY: 3 AN XY: 71542

Gnomad4 AFR AF: 0.0000245

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000988

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000116

Gnomad4 NFE AF: 0.0000303

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

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: rs926747893; hg19: chr7-153750071;