rs1248688

Variant summary

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

The NM_004747.4(DLG5):​c.864+2059C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,176 control chromosomes in the GnomAD database, including 5,494 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 0.25 ( 5494 hom., cov: 33)

Consequence

DLG5
NM_004747.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.178

Publications

5 publications found
Variant links:
Genes affected
DLG5 (HGNC:2904): (discs large MAGUK scaffold protein 5) This gene encodes a member of the family of discs large (DLG) homologs, a subset of the membrane-associated guanylate kinase (MAGUK) superfamily. The MAGUK proteins are composed of a catalytically inactive guanylate kinase domain, in addition to PDZ and SH3 domains, and are thought to function as scaffolding molecules at sites of cell-cell contact. The protein encoded by this gene localizes to the plasma membrane and cytoplasm, and interacts with components of adherens junctions and the cytoskeleton. It is proposed to function in the transmission of extracellular signals to the cytoskeleton and in the maintenance of epithelial cell structure. Alternative splice variants have been described but their biological nature has not been determined. [provided by RefSeq, Jul 2008]
DLG5 Gene-Disease associations (from GenCC):
  • Yuksel-Vogel-Bauer syndrome
    Inheritance: AD, AR Classification: LIMITED Submitted by: G2P
  • ciliopathy
    Inheritance: AR, AD Classification: LIMITED Submitted by: Franklin by Genoox
  • congenital anomaly of kidney and urinary tract
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

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=-0.86).
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DLG5NM_004747.4 linkc.864+2059C>T intron_variant Intron 5 of 31 ENST00000372391.7 NP_004738.3 Q8TDM6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DLG5ENST00000372391.7 linkc.864+2059C>T intron_variant Intron 5 of 31 1 NM_004747.4 ENSP00000361467.2 Q8TDM6-1
DLG5ENST00000468332.6 linkn.639+2059C>T intron_variant Intron 5 of 29 2 ENSP00000473298.1 R4GMQ2
DLG5ENST00000475613.6 linkn.93+17804C>T intron_variant Intron 1 of 21 5

Frequencies

GnomAD3 genomes
AF:
0.254
AC:
38694
AN:
152058
Hom.:
5486
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.151
Gnomad AMI
AF:
0.175
Gnomad AMR
AF:
0.386
Gnomad ASJ
AF:
0.177
Gnomad EAS
AF:
0.309
Gnomad SAS
AF:
0.298
Gnomad FIN
AF:
0.309
Gnomad MID
AF:
0.244
Gnomad NFE
AF:
0.277
Gnomad OTH
AF:
0.239
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.254
AC:
38708
AN:
152176
Hom.:
5494
Cov.:
33
AF XY:
0.260
AC XY:
19308
AN XY:
74384
show subpopulations
African (AFR)
AF:
0.151
AC:
6270
AN:
41536
American (AMR)
AF:
0.387
AC:
5916
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.177
AC:
616
AN:
3472
East Asian (EAS)
AF:
0.308
AC:
1597
AN:
5178
South Asian (SAS)
AF:
0.300
AC:
1447
AN:
4830
European-Finnish (FIN)
AF:
0.309
AC:
3270
AN:
10570
Middle Eastern (MID)
AF:
0.241
AC:
71
AN:
294
European-Non Finnish (NFE)
AF:
0.277
AC:
18861
AN:
67986
Other (OTH)
AF:
0.237
AC:
500
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1465
2930
4395
5860
7325
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
400
800
1200
1600
2000
<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:
0.271
Hom.:
2951
Bravo
AF:
0.254
Asia WGS
AF:
0.321
AC:
1119
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
2.5
DANN
Benign
0.72
PhyloP100
-0.18
Mutation Taster
=100/0
polymorphism (auto)

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: rs1248688; hg19: chr10-79611053; API