rs3807218

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_130797.4(DPP6):c.723A>G(p.Lys241Lys) 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, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.500

Publications

26 publications found

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 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

DPP6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 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 VariationId is 1174770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
DPP6	NM_130797.4 link	c.723A>G	p.Lys241Lys	synonymous_variant	Exon 7 of 26	ENST00000377770.8	NP_570629.2	P42658-1Q8IYG9A7E2E4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8 link	c.723A>G	p.Lys241Lys	synonymous_variant	Exon 7 of 26	1	NM_130797.4	ENSP00000367001.3		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

GnomAD2 exomes

AF:

0.869

AC:

145053

AN:

166836

AF XY:

0.875

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 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

African (AFR)

AF:

0.665

AC:

21245

AN:

31940

American (AMR)

AF:

0.845

AC:

30659

AN:

36272

Ashkenazi Jewish (ASJ)

AF:

0.845

AC:

21331

AN:

25230

East Asian (EAS)

AF:

0.851

AC:

30992

AN:

36416

South Asian (SAS)

AF:

0.871

AC:

69227

AN:

79452

European-Finnish (FIN)

AF:

0.898

AC:

44697

AN:

49790

Middle Eastern (MID)

AF:

0.870

AC:

4961

AN:

5704

European-Non Finnish (NFE)

AF:

0.907

AC:

981124

AN:

1081576

Other (OTH)

AF:

0.877

AC:

51079

AN:

58270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

7845

15690

23534

31379

39224

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21108

42216

63324

84432

105540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.828

AC:

126041

AN:

152204

Hom.:

52939

Cov.:

AF XY:

0.828

AC XY:

61647

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.670

AC:

27788

AN:

41490

American (AMR)

AF:

0.842

AC:

12882

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.849

AC:

2946

AN:

3472

East Asian (EAS)

AF:

0.842

AC:

4362

AN:

5178

South Asian (SAS)

AF:

0.851

AC:

4099

AN:

4816

European-Finnish (FIN)

AF:

0.901

AC:

9548

AN:

10602

Middle Eastern (MID)

AF:

0.867

AC:

255

AN:

294

European-Non Finnish (NFE)

AF:

0.905

AC:

61584

AN:

68022

Other (OTH)

AF:

0.827

AC:

1749

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1047

2094

3141

4188

5235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.881

Hom.:

267142

Bravo

AF:

0.819

Asia WGS

AF:

0.813

AC:

2828

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

Benign:1

Aug 11, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.2

(source)

DANN

Benign

0.53

PhyloP100

-0.50

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over