rs11243354

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000496611.2(DPP6):​c.*350T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,007,696 control chromosomes in the GnomAD database, including 23,340 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6990 hom., cov: 32)
Exomes 𝑓: 0.18 ( 16350 hom. )

Consequence

DPP6
ENST00000496611.2 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0380

Publications

2 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 7-154587524-T-C is Benign according to our data. Variant chr7-154587524-T-C is described in ClinVar as [Benign]. Clinvar id is 1237202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DPP6NM_130797.4 linkc.627+20608T>C intron_variant Intron 5 of 25 ENST00000377770.8 NP_570629.2 P42658-1Q8IYG9A7E2E4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DPP6ENST00000377770.8 linkc.627+20608T>C intron_variant Intron 5 of 25 1 NM_130797.4 ENSP00000367001.3 P42658-1

Frequencies

GnomAD3 genomes
AF:
0.266
AC:
40351
AN:
151670
Hom.:
6969
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.496
Gnomad AMI
AF:
0.212
Gnomad AMR
AF:
0.264
Gnomad ASJ
AF:
0.137
Gnomad EAS
AF:
0.0853
Gnomad SAS
AF:
0.154
Gnomad FIN
AF:
0.147
Gnomad MID
AF:
0.187
Gnomad NFE
AF:
0.176
Gnomad OTH
AF:
0.233
GnomAD4 exome
AF:
0.184
AC:
157485
AN:
855908
Hom.:
16350
Cov.:
11
AF XY:
0.183
AC XY:
78904
AN XY:
431360
show subpopulations
African (AFR)
AF:
0.515
AC:
10742
AN:
20876
American (AMR)
AF:
0.240
AC:
5841
AN:
24328
Ashkenazi Jewish (ASJ)
AF:
0.145
AC:
2470
AN:
16982
East Asian (EAS)
AF:
0.0689
AC:
2277
AN:
33056
South Asian (SAS)
AF:
0.166
AC:
9187
AN:
55302
European-Finnish (FIN)
AF:
0.156
AC:
4736
AN:
30278
Middle Eastern (MID)
AF:
0.165
AC:
725
AN:
4400
European-Non Finnish (NFE)
AF:
0.180
AC:
113493
AN:
630992
Other (OTH)
AF:
0.202
AC:
8014
AN:
39694
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
6787
13574
20361
27148
33935
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
3450
6900
10350
13800
17250
<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:
0.266
AC:
40423
AN:
151788
Hom.:
6990
Cov.:
32
AF XY:
0.262
AC XY:
19434
AN XY:
74196
show subpopulations
African (AFR)
AF:
0.496
AC:
20490
AN:
41298
American (AMR)
AF:
0.264
AC:
4024
AN:
15256
Ashkenazi Jewish (ASJ)
AF:
0.137
AC:
475
AN:
3466
East Asian (EAS)
AF:
0.0851
AC:
436
AN:
5124
South Asian (SAS)
AF:
0.154
AC:
740
AN:
4804
European-Finnish (FIN)
AF:
0.147
AC:
1547
AN:
10548
Middle Eastern (MID)
AF:
0.194
AC:
57
AN:
294
European-Non Finnish (NFE)
AF:
0.176
AC:
11974
AN:
67980
Other (OTH)
AF:
0.231
AC:
487
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.510
Heterozygous variant carriers
0
1351
2703
4054
5406
6757
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
370
740
1110
1480
1850
<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:
0.207
Hom.:
792
Bravo
AF:
0.284
Asia WGS
AF:
0.147
AC:
510
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

May 11, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.72
DANN
Benign
0.46
PhyloP100
0.038

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

Other links and lift over

dbSNP: rs11243354; hg19: chr7-154379234; API