Genetic Variant DPP6:p.Lys241Asn (chr7-154669402-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_130797.4(DPP6):c.723A>T(p.Lys241Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K241K) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DPP6
NM_130797.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23458529).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130797.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DPP6	NM_130797.4	MANE Select	c.723A>T	p.Lys241Asn	missense	Exon 7 of 26	NP_570629.2
DPP6	NM_001364497.2		c.540A>T	p.Lys180Asn	missense	Exon 8 of 27	NP_001351426.1
DPP6	NM_001364498.2		c.540A>T	p.Lys180Asn	missense	Exon 8 of 27	NP_001351427.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DPP6	ENST00000377770.8	TSL:1 MANE Select	c.723A>T	p.Lys241Asn	missense	Exon 7 of 26	ENSP00000367001.3
DPP6	ENST00000332007.7	TSL:1	c.537A>T	p.Lys179Asn	missense	Exon 7 of 26	ENSP00000328226.3
DPP6	ENST00000404039.5	TSL:1	c.531A>T	p.Lys177Asn	missense	Exon 7 of 26	ENSP00000385578.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1404718

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693260

African (AFR)

AF:

0.00

AC:

AN:

31946

American (AMR)

AF:

0.00

AC:

AN:

36282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25230

East Asian (EAS)

AF:

0.00

AC:

AN:

36422

South Asian (SAS)

AF:

0.00

AC:

AN:

79468

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49794

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1081598

Other (OTH)

AF:

0.00

AC:

AN:

58274

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

267142

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.64

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0082

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.053

M_CAP

Benign

0.0087

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

PhyloP100

-0.50

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-1.2

REVEL

Benign

0.16

Sift

Benign

0.22

Sift4G

Benign

0.49

Polyphen

0.88

Vest4

0.36

MutPred

0.43

Loss of ubiquitination at K241 (P = 0.0103)

MVP

0.19

MPC

1.2

ClinPred

0.69

GERP RS

-8.3

Varity_R

0.30

gMVP

0.46

Mutation Taster

=56/44

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over