dbSNP rs11767658: DPP6:c.680+2662T>A (chr7-154640535-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_130797.4(DPP6):c.680+2662T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,968 control chromosomes in the GnomAD database, including 10,587 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 0.37 ( 10587 hom., cov: 32)

Consequence

DPP6
NM_130797.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.688

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPP6	NM_130797.4 link	c.680+2662T>A		intron_variant	Intron 6 of 25	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.680+2662T>A		intron_variant	Intron 6 of 25	1	NM_130797.4	ENSP00000367001.3		P42658-1

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56295

AN:

151850

Hom.:

10582

Cov.:

show subpopulations

Gnomad AFR

AF:

0.402

Gnomad AMI

AF:

0.455

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.246

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.368

Gnomad OTH

AF:

0.353

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

GnomAD4 genome

AF:

0.371

AC:

56326

AN:

151968

Hom.:

10587

Cov.:

AF XY:

0.369

AC XY:

27412

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.401

AC:

16633

AN:

41442

American (AMR)

AF:

0.327

AC:

4993

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

1573

AN:

3466

East Asian (EAS)

AF:

0.246

AC:

1265

AN:

5140

South Asian (SAS)

AF:

0.279

AC:

1343

AN:

4818

European-Finnish (FIN)

AF:

0.405

AC:

4269

AN:

10550

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.368

AC:

24985

AN:

67968

Other (OTH)

AF:

0.352

AC:

745

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1802

3603

5405

7206

9008

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

542

1084

1626

2168

2710

<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:

0.255

Hom.:

618

Bravo

AF:

0.368

Asia WGS

AF:

0.292

AC:

1014

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.0

(source)

DANN

Benign

0.77

PhyloP100

0.69

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over