7-154052986-C-CGCG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_130797.4(DPP6):c.185_187dup(p.Gly62dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00539 in 146,922 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (2 hom., cov: 31)
  • Exomes 𝑓: 0.0033 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: DPP6 NM_130797.4 inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• 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 -6 ACMG points.

• BP6: Variant 7-154052986-C-CGCG is Benign according to our data. Variant chr7-154052986-C-CGCG is described in ClinVar as [Likely_benign]. Clinvar id is 810229.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 791 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4	c.185_187dup	p.Gly62dup	inframe_insertion	1/26	ENST00000377770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8	c.185_187dup	p.Gly62dup	inframe_insertion	1/26	1	NM_130797.4
DPP6	ENST00000406326.5	c.185_187dup	p.Gly62dup	inframe_insertion	1/6	1
DPP6	ENST00000404039.5	c.51+165271_51+165273dup		intron_variant		1
DPP6	ENST00000706130.1	c.60+303997_60+303999dup		intron_variant

Frequencies

GnomAD3 genomes AF: 0.00539 AC: 791 AN: 146826 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00588

Gnomad ASJ AF: 0.00382

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00292

Gnomad FIN AF: 0.00510

Gnomad MID AF: 0.00649

Gnomad NFE AF: 0.00797

Gnomad OTH AF: 0.00936

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00331 AC: 3076 AN: 929656 Hom.: 1 Cov.: 37 AF XY: 0.00320 AC XY: 1392 AN XY: 435672

Gnomad4 AFR exome AF: 0.00192

Gnomad4 AMR exome AF: 0.00132

Gnomad4 ASJ exome AF: 0.00109

Gnomad4 EAS exome AF: 0.000155

Gnomad4 SAS exome AF: 0.00337

Gnomad4 FIN exome AF: 0.000917

Gnomad4 NFE exome AF: 0.00346

Gnomad4 OTH exome AF: 0.00319

GnomAD4 genome AF: 0.00539 AC: 792 AN: 146922 Hom.: 2 Cov.: 31 AF XY: 0.00562 AC XY: 402 AN XY: 71546

Gnomad4 AFR AF: 0.00208

Gnomad4 AMR AF: 0.00587

Gnomad4 ASJ AF: 0.00382

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.00292

Gnomad4 FIN AF: 0.00510

Gnomad4 NFE AF: 0.00797

Gnomad4 OTH AF: 0.00926

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	DPP6: BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not specified Benign:1

Benign, no assertion criteria provided

clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

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Computational scores

Source: dbNSFP v4.3

Splicing

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;