rs7779540

Variant names:

• chr7-153925577-G-A
• rs7779540
• ENST00000404039.5:c.51+37843G>A

Variant summary

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

The ENST00000404039.5(DPP6):​c.51+37843G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 151,920 control chromosomes in the GnomAD database, including 350 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 0.066 (350 hom., cov: 31)
• Consequence: DPP6 ENST00000404039.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81
• 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=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_001364497.2	c.60+176569G>A		intron_variant	Intron 2 of 26		NP_001351426.1
DPP6	NM_001364498.2	c.60+176569G>A		intron_variant	Intron 2 of 26		NP_001351427.1
DPP6	NM_001364499.2	c.60+176569G>A		intron_variant	Intron 2 of 26		NP_001351428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000404039.5	c.51+37843G>A		intron_variant	Intron 1 of 25	1		ENSP00000385578.1
DPP6	ENST00000706130.1	c.60+176569G>A		intron_variant	Intron 2 of 26			ENSP00000516215.1

Frequencies

GnomAD3 genomes AF: 0.0657 AC: 9975 AN: 151798 Hom.: 350 Cov.: 31

Gnomad AFR AF: 0.0853

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0407

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.0511

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.0630

Gnomad OTH AF: 0.0599

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

GnomAD4 genome AF: 0.0657 AC: 9981 AN: 151920 Hom.: 350 Cov.: 31 AF XY: 0.0633 AC XY: 4701 AN XY: 74218

African (AFR) AF: 0.0851 AC: 3525 AN: 41442

American (AMR) AF: 0.0600 AC: 916 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.0406 AC: 207 AN: 5100

South Asian (SAS) AF: 0.0241 AC: 116 AN: 4812

European-Finnish (FIN) AF: 0.0511 AC: 540 AN: 10562

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0631 AC: 4285 AN: 67956

Other (OTH) AF: 0.0602 AC: 127 AN: 2110

Alfa AF: 0.0604 Hom.: 469

Bravo AF: 0.0679

Asia WGS AF: 0.0440 AC: 153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	5.6
DANN	Benign	0.51
PhyloP100		2.8

Splicing

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

Other links and lift over

dbSNP: rs7779540; hg19: chr7-153622662;