Genetic Variant DPP6:c.-153C>G (chr7-154052668-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_130797.4(DPP6):c.-153C>G variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DPP6
NM_130797.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.508

Publications

4 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
ventricular fibrillation, paroxysmal familial, 2
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
intellectual disability, autosomal dominant 33
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
complex neurodevelopmental disorder
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

DPP6 links:

ENSG00000203335 (HGNC:):

ENSG00000203335 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

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	Effect	Exon Rank	Protein	UniProt
DPP6	NM_130797.4	MANE Select	c.-153C>G	5_prime_UTR	Exon 1 of 26	NP_570629.2	P42658-1
DPP6	NM_001290253.2		c.-153C>G	5_prime_UTR	Exon 1 of 6	NP_001277182.1	Q8IYG9
DPP6	NM_001364497.2		c.60+303660C>G	intron	N/A	NP_001351426.1	A0A994J7K0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DPP6	ENST00000377770.8	TSL:1 MANE Select	c.-153C>G	5_prime_UTR	Exon 1 of 26	ENSP00000367001.3	P42658-1
DPP6	ENST00000406326.5	TSL:1	c.-153C>G	5_prime_UTR	Exon 1 of 6	ENSP00000384393.1	Q8IYG9
DPP6	ENST00000404039.5	TSL:1	c.51+164934C>G	intron	N/A	ENSP00000385578.1	E9PF59

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1070970

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

516916

African (AFR)

AF:

0.00

AC:

AN:

20266

American (AMR)

AF:

0.00

AC:

AN:

12912

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12030

East Asian (EAS)

AF:

0.00

AC:

AN:

17822

South Asian (SAS)

AF:

0.00

AC:

AN:

49676

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14826

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2656

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

901308

Other (OTH)

AF:

0.00

AC:

AN:

39474

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

2765

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

-0.51

PromoterAI

-0.00040

Neutral

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over