NM_130797.4:c.762+21586G>A

Variant names:

• chr7-154691027-G-A
• rs3807243
• NM_130797.4:c.762+21586G>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.762+21586G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,034 control chromosomes in the GnomAD database, including 2,519 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 0.16 (2519 hom., cov: 33)
• Consequence: DPP6 NM_130797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_130797.4	c.762+21586G>A		intron_variant	Intron 7 of 25	ENST00000377770.8	NP_570629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8	c.762+21586G>A		intron_variant	Intron 7 of 25	1	NM_130797.4	ENSP00000367001.3

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24821 AN: 151916 Hom.: 2507 Cov.: 33

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0765

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.164 AC: 24861 AN: 152034 Hom.: 2519 Cov.: 33 AF XY: 0.161 AC XY: 11940 AN XY: 74344

African (AFR) AF: 0.288 AC: 11949 AN: 41454

American (AMR) AF: 0.104 AC: 1594 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 425 AN: 3470

East Asian (EAS) AF: 0.0763 AC: 396 AN: 5192

South Asian (SAS) AF: 0.135 AC: 651 AN: 4826

European-Finnish (FIN) AF: 0.122 AC: 1293 AN: 10588

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8099 AN: 67942

Other (OTH) AF: 0.133 AC: 280 AN: 2112

Alfa AF: 0.164 Hom.: 394

Bravo AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.2
DANN	Benign	0.66
PhyloP100		-0.16

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: rs3807243; hg19: chr7-154482737;