rs569787719

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_130797.4(DPP6):c.226G>A(p.Asp76Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0226 in 1,058,538 control chromosomes in the GnomAD database, including 312 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D76V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.016 ( 26 hom., cov: 31)

Exomes 𝑓: 0.024 ( 286 hom. )

Consequence

DPP6
NM_130797.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.63

Publications

5 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:

ENSG00000203335 (HGNC:):

ENSG00000203335 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023885071).

BP6

Variant 7-154053046-G-A is Benign according to our data. Variant chr7-154053046-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 377138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0161 (2407/149904) while in subpopulation SAS AF = 0.0288 (137/4760). AF 95% confidence interval is 0.0249. There are 26 homozygotes in GnomAd4. There are 1253 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 2407 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_130797.4 link	c.226G>A	p.Asp76Asn	missense_variant	Exon 1 of 26	ENST00000377770.8	NP_570629.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPP6	ENST00000377770.8 link	c.226G>A	p.Asp76Asn	missense_variant	Exon 1 of 26	1	NM_130797.4	ENSP00000367001.3

Frequencies

GnomAD3 genomes

AF:

0.0161

AC:

2406

AN:

149792

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00402

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0135

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0285

Gnomad FIN

AF:

0.0367

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0215

Gnomad OTH

AF:

0.0155

GnomAD2 exomes

AF:

0.0286

AC:

AN:

2200

AF XY:

0.0297

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0364

Gnomad NFE exome

AF:

0.0297

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0237

AC:

21490

AN:

908634

Hom.:

286

Cov.:

AF XY:

0.0236

AC XY:

10017

AN XY:

424422

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

17744

American (AMR)

AF:

0.00804

AC:

AN:

2984

Ashkenazi Jewish (ASJ)

AF:

0.00953

AC:

AN:

7558

East Asian (EAS)

AF:

0.0000901

AC:

AN:

11096

South Asian (SAS)

AF:

0.0312

AC:

565

AN:

18124

European-Finnish (FIN)

AF:

0.0261

AC:

223

AN:

8542

Middle Eastern (MID)

AF:

0.0153

AC:

AN:

2154

European-Non Finnish (NFE)

AF:

0.0245

AC:

19781

AN:

808678

Other (OTH)

AF:

0.0236

AC:

750

AN:

31754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

1289

2577

3866

5154

6443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1008

2016

3024

4032

5040

<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:

0.0161

AC:

2407

AN:

149904

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1253

AN XY:

73148

show subpopulations

African (AFR)

AF:

0.00401

AC:

165

AN:

41124

American (AMR)

AF:

0.0134

AC:

202

AN:

15052

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5002

South Asian (SAS)

AF:

0.0288

AC:

137

AN:

4760

European-Finnish (FIN)

AF:

0.0367

AC:

363

AN:

9882

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0215

AC:

1449

AN:

67334

Other (OTH)

AF:

0.0153

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

109

219

328

438

547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00577

Hom.:

Bravo

AF:

0.0131

ExAC

AF:

0.00978

AC:

134

Asia WGS

AF:

0.00956

AC:

AN:

3466

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 10, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.021

T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.58

MetaRNN

Benign

0.0024

T;T

MetaSVM

Benign

-0.92

PhyloP100

3.6

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0070

D;T

Sift4G

Benign

0.15

T;T

Polyphen

1.0

D;B

Vest4

0.13

MPC

0.42

ClinPred

0.072

GERP RS

2.3

Varity_R

0.11

gMVP

0.10

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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