Genetic Variant DPP6:p.Leu44Leu (chr7-154052952-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_130797.4(DPP6):c.132C>T(p.Leu44Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000853 in 1,218,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

DPP6
NM_130797.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.964

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 7-154052952-C-T is Benign according to our data. Variant chr7-154052952-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2658248.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.964 with no splicing effect.

BS2

High AC in GnomAd4 at 42 AD,Unknown gene.

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	UniProt
DPP6	NM_130797.4	MANE Select	c.132C>T	p.Leu44Leu	synonymous	Exon 1 of 26	NP_570629.2	P42658-1
DPP6	NM_001290253.2		c.132C>T	p.Leu44Leu	synonymous	Exon 1 of 6	NP_001277182.1	Q8IYG9
DPP6	NM_001364497.2		c.60+303944C>T		intron	N/A	NP_001351426.1	A0A994J7K0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DPP6	ENST00000377770.8	TSL:1 MANE Select	c.132C>T	p.Leu44Leu	synonymous	Exon 1 of 26	ENSP00000367001.3	P42658-1
DPP6	ENST00000406326.5	TSL:1	c.132C>T	p.Leu44Leu	synonymous	Exon 1 of 6	ENSP00000384393.1	Q8IYG9
DPP6	ENST00000404039.5	TSL:1	c.51+165218C>T		intron	N/A	ENSP00000385578.1	E9PF59

Frequencies

GnomAD3 genomes

AF:

0.000285

AC:

AN:

147384

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000807

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000337

Gnomad ASJ

AF:

0.000294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000301

Gnomad OTH

AF:

0.000494

GnomAD2 exomes

AF:

0.000184

AC:

AN:

49034

AF XY:

0.000136

show subpopulations

Gnomad AFR exome

AF:

0.00460

Gnomad AMR exome

AF:

0.000822

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000579

AC:

AN:

1071032

Hom.:

Cov.:

AF XY:

0.0000523

AC XY:

AN XY:

516694

show subpopulations

African (AFR)

AF:

0.00106

AC:

AN:

21664

American (AMR)

AF:

0.000444

AC:

AN:

13518

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15378

East Asian (EAS)

AF:

0.00

AC:

AN:

18506

South Asian (SAS)

AF:

0.00

AC:

AN:

39156

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18974

Middle Eastern (MID)

AF:

0.000696

AC:

AN:

2874

European-Non Finnish (NFE)

AF:

0.0000255

AC:

AN:

900698

Other (OTH)

AF:

0.000199

AC:

AN:

40264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000285

AC:

AN:

147488

Hom.:

Cov.:

AF XY:

0.000320

AC XY:

AN XY:

71848

show subpopulations

African (AFR)

AF:

0.000805

AC:

AN:

41000

American (AMR)

AF:

0.000337

AC:

AN:

14852

Ashkenazi Jewish (ASJ)

AF:

0.000294

AC:

AN:

3398

East Asian (EAS)

AF:

0.00

AC:

AN:

5068

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8762

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000301

AC:

AN:

66348

Other (OTH)

AF:

0.000489

AC:

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000142

Hom.:

Bravo

AF:

0.000276

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.7

(source)

DANN

Uncertain

0.98

PhyloP100

-0.96

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over