rs38993

Variant names:

• chr7-153879172-G-A
• rs38993
• NM_001364497.2:c.60+130164G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001364497.2(DPP6):​c.60+130164G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 151,702 control chromosomes in the GnomAD database, including 27,754 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 0.60 (27754 hom., cov: 30)
• Consequence: DPP6 NM_001364497.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110
• Publications: 7 publications found

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]

DPP6 Gene-Disease associations (from GenCC):

• autosomal dominant primary microcephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• paroxysmal familial ventricular fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, autosomal dominant 33

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• ventricular fibrillation, paroxysmal familial, 2

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_001364497.2	c.60+130164G>A		intron_variant	Intron 2 of 26		NP_001351426.1
DPP6	NM_001364498.2	c.60+130164G>A		intron_variant	Intron 2 of 26		NP_001351427.1
DPP6	NM_001364499.2	c.60+130164G>A		intron_variant	Intron 2 of 26		NP_001351428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000706130.1	c.60+130164G>A		intron_variant	Intron 2 of 26			ENSP00000516215.1

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91119 AN: 151584 Hom.: 27728 Cov.: 30

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.601 AC: 91194 AN: 151702 Hom.: 27754 Cov.: 30 AF XY: 0.592 AC XY: 43909 AN XY: 74114

African (AFR) AF: 0.672 AC: 27742 AN: 41312

American (AMR) AF: 0.545 AC: 8307 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2002 AN: 3468

East Asian (EAS) AF: 0.431 AC: 2208 AN: 5128

South Asian (SAS) AF: 0.554 AC: 2648 AN: 4782

European-Finnish (FIN) AF: 0.482 AC: 5081 AN: 10538

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41077 AN: 67918

Other (OTH) AF: 0.579 AC: 1220 AN: 2106

Alfa AF: 0.603 Hom.: 15572

Bravo AF: 0.608

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.48
PhyloP100		0.11

Splicing

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

Other links and lift over

dbSNP: rs38993; hg19: chr7-153576257;