rs3807218

Positions:

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_130797.4(DPP6):c.723A>G(p.Lys241=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 1,556,854 control chromosomes in the GnomAD database, including 615,219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.83 ( 52939 hom., cov: 33)

Exomes 𝑓: 0.89 ( 562280 hom. )

Consequence

DPP6
NM_130797.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:4

Conservation

PhyloP100: -0.500

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-154669402-A-G is Benign according to our data. Variant chr7-154669402-A-G is described in ClinVar as [Benign]. Clinvar id is 1174770.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-154669402-A-G is described in Lovd as [Likely_benign]. Variant chr7-154669402-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.5 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DPP6	NM_130797.4 linkuse as main transcript	c.723A>G	p.Lys241=	synonymous_variant	7/26	ENST00000377770.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DPP6	ENST00000377770.8 linkuse as main transcript	c.723A>G	p.Lys241=	synonymous_variant	7/26	1	NM_130797.4		P42658-1

Frequencies

GnomAD3 genomes

AF:

0.828

AC:

125976

AN:

152086

Hom.:

52918

Cov.:

show subpopulations

Gnomad AFR

AF:

0.670

Gnomad AMI

AF:

0.910

Gnomad AMR

AF:

0.842

Gnomad ASJ

AF:

0.849

Gnomad EAS

AF:

0.842

Gnomad SAS

AF:

0.851

Gnomad FIN

AF:

0.901

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.905

Gnomad OTH

AF:

0.830

GnomAD3 exomes

AF:

0.869

AC:

145053

AN:

166836

Hom.:

63394

AF XY:

0.875

AC XY:

76902

AN XY:

87918

show subpopulations

Gnomad AFR exome

AF:

0.666

Gnomad AMR exome

AF:

0.846

Gnomad ASJ exome

AF:

0.848

Gnomad EAS exome

AF:

0.847

Gnomad SAS exome

AF:

0.871

Gnomad FIN exome

AF:

0.892

Gnomad NFE exome

AF:

0.905

Gnomad OTH exome

AF:

0.882

GnomAD4 exome

AF:

0.894

AC:

1255315

AN:

1404650

Hom.:

562280

Cov.:

AF XY:

0.893

AC XY:

619288

AN XY:

693224

show subpopulations

Gnomad4 AFR exome

AF:

0.665

Gnomad4 AMR exome

AF:

0.845

Gnomad4 ASJ exome

AF:

0.845

Gnomad4 EAS exome

AF:

0.851

Gnomad4 SAS exome

AF:

0.871

Gnomad4 FIN exome

AF:

0.898

Gnomad4 NFE exome

AF:

0.907

Gnomad4 OTH exome

AF:

0.877

GnomAD4 genome

AF:

0.828

AC:

126041

AN:

152204

Hom.:

52939

Cov.:

AF XY:

0.828

AC XY:

61647

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.670

Gnomad4 AMR

AF:

0.842

Gnomad4 ASJ

AF:

0.849

Gnomad4 EAS

AF:

0.842

Gnomad4 SAS

AF:

0.851

Gnomad4 FIN

AF:

0.901

Gnomad4 NFE

AF:

0.905

Gnomad4 OTH

AF:

0.827

Alfa

AF:

0.888

Hom.:

136854

Bravo

AF:

0.819

Asia WGS

AF:

0.813

AC:

2828

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Ventricular fibrillation, paroxysmal familial, 2;C4225375:Intellectual disability, autosomal dominant 33

Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.2

DANN

Benign

0.53

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over