NM_130797.4:c.226G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -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. 12/18 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 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

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 -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 id is 377138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-154053046-G-A is described in Lovd as [Benign].

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 male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2407 AD 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	P42658-1Q8IYG9A7E2E4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DPP6	ENST00000377770.8 link	c.226G>A	p.Asp76Asn	missense_variant	Exon 1 of 26	1	NM_130797.4	ENSP00000367001.3	P42658-1
DPP6	ENST00000406326.5 link	c.226G>A	p.Asp76Asn	missense_variant	Exon 1 of 6	1		ENSP00000384393.1	Q8IYG9
DPP6	ENST00000404039.5 link	c.51+165312G>A		intron_variant	Intron 1 of 25	1		ENSP00000385578.1	E9PF59
DPP6	ENST00000706130.1 link	c.60+304038G>A		intron_variant	Intron 2 of 26			ENSP00000516215.1	A0A994J7K0

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

GnomAD3 exomes

AF:

0.0286

AC:

AN:

2200

Hom.:

AF XY:

0.0297

AC XY:

AN XY:

1312

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 SAS exome

AF:

0.0208

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

Gnomad4 AFR exome

AF:

0.00231

Gnomad4 AMR exome

AF:

0.00804

Gnomad4 ASJ exome

AF:

0.00953

Gnomad4 EAS exome

AF:

0.0000901

Gnomad4 SAS exome

AF:

0.0312

Gnomad4 FIN exome

AF:

0.0261

Gnomad4 NFE exome

AF:

0.0245

Gnomad4 OTH exome

AF:

0.0236

GnomAD4 genome

AF:

0.0161

AC:

2407

AN:

149904

Hom.:

Cov.:

AF XY:

0.0171

AC XY:

1253

AN XY:

73148

show subpopulations

Gnomad4 AFR

AF:

0.00401

Gnomad4 AMR

AF:

0.0134

Gnomad4 ASJ

AF:

0.0124

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0288

Gnomad4 FIN

AF:

0.0367

Gnomad4 NFE

AF:

0.0215

Gnomad4 OTH

AF:

0.0153

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

- -

Clinical Genetics, Academic Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

- -

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

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

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

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