NM_130797.4:c.628-15521G>A

Variant names:

• chr7-154622300-G-A
• rs2046748
• NM_130797.4:c.628-15521G>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.628-15521G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 152,154 control chromosomes in the GnomAD database, including 53,454 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 0.83 (53454 hom., cov: 32)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 2 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

LOC105375581 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.89 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.628-15521G>A		intron	N/A	NP_570629.2
	DPP6	NM_001364497.2		c.445-15521G>A		intron	N/A	NP_001351426.1
	DPP6	NM_001364498.2		c.445-15521G>A		intron	N/A	NP_001351427.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DPP6	ENST00000377770.8	TSL:1 MANE Select	c.628-15521G>A		intron	N/A	ENSP00000367001.3
	DPP6	ENST00000332007.7	TSL:1	c.442-15521G>A		intron	N/A	ENSP00000328226.3
	DPP6	ENST00000404039.5	TSL:1	c.436-15521G>A		intron	N/A	ENSP00000385578.1

Frequencies

GnomAD3 genomes AF: 0.833 AC: 126584 AN: 152036 Hom.: 53431 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.896

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.832 AC: 126654 AN: 152154 Hom.: 53454 Cov.: 32 AF XY: 0.828 AC XY: 61555 AN XY: 74384

African (AFR) AF: 0.763 AC: 31685 AN: 41500

American (AMR) AF: 0.834 AC: 12748 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3250 AN: 3472

East Asian (EAS) AF: 0.436 AC: 2243 AN: 5150

South Asian (SAS) AF: 0.685 AC: 3296 AN: 4812

European-Finnish (FIN) AF: 0.917 AC: 9727 AN: 10608

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.896 AC: 60924 AN: 68004

Other (OTH) AF: 0.844 AC: 1783 AN: 2112

Alfa AF: 0.872 Hom.: 108424

Bravo AF: 0.825

Asia WGS AF: 0.605 AC: 2104 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.79
PhyloP100		-0.31

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

Other links and lift over

dbSNP: rs2046748; hg19: chr7-154414010;