rs7780487

Variant names:

• chr7-154314899-G-A
• rs7780487
• NM_130797.4:c.244-131315G>A

Variant summary

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

The NM_130797.4(DPP6):​c.244-131315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 152,068 control chromosomes in the GnomAD database, including 20,946 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 0.51 (20946 hom., cov: 33)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.274
• Publications: 4 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
• ventricular fibrillation, paroxysmal familial, 2

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• intellectual disability, autosomal dominant 33

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130797.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	NM_130797.4	MANE Select	c.244-131315G>A		intron	N/A	NP_570629.2	P42658-1
	DPP6	NM_001364497.2		c.61-131315G>A		intron	N/A	NP_001351426.1	A0A994J7K0
	DPP6	NM_001364498.2		c.61-131315G>A		intron	N/A	NP_001351427.1	A0A994J7K0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000377770.8	TSL:1 MANE Select	c.244-131315G>A		intron	N/A	ENSP00000367001.3	P42658-1
	DPP6	ENST00000332007.7	TSL:1	c.57+9348G>A		intron	N/A	ENSP00000328226.3	P42658-2
	DPP6	ENST00000404039.5	TSL:1	c.52-131315G>A		intron	N/A	ENSP00000385578.1	E9PF59

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76831 AN: 151950 Hom.: 20949 Cov.: 33

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.505 AC: 76839 AN: 152068 Hom.: 20946 Cov.: 33 AF XY: 0.510 AC XY: 37887 AN XY: 74330

African (AFR) AF: 0.289 AC: 11971 AN: 41486

American (AMR) AF: 0.517 AC: 7901 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2187 AN: 3470

East Asian (EAS) AF: 0.659 AC: 3400 AN: 5158

South Asian (SAS) AF: 0.579 AC: 2784 AN: 4810

European-Finnish (FIN) AF: 0.596 AC: 6302 AN: 10574

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40644 AN: 67966

Other (OTH) AF: 0.510 AC: 1078 AN: 2114

Alfa AF: 0.566 Hom.: 40455

Bravo AF: 0.484

Asia WGS AF: 0.560 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.73
PhyloP100		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7780487; hg19: chr7-154011984;