Variant rs2289308 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004747.4(DLG5):c.3527-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,599,250 control chromosomes in the GnomAD database, including 84,406 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 0.27 ( 6099 hom., cov: 31)

Exomes 𝑓: 0.33 ( 78307 hom. )

Consequence

DLG5
NM_004747.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.69

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 links:

DLG5 (HGNC:):

DLG5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG5	NM_004747.4 linkuse as main transcript	c.3527-28C>T		intron_variant		ENST00000372391.7	NP_004738.3	Q8TDM6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7 linkuse as main transcript	c.3527-28C>T		intron_variant		1	NM_004747.4	ENSP00000361467.2		Q8TDM6-1

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40461

AN:

151804

Hom.:

6101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.596

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.284

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.297

GnomAD3 exomes

AF:

0.292

AC:

69339

AN:

237826

Hom.:

10699

AF XY:

0.298

AC XY:

38320

AN XY:

128494

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.237

Gnomad ASJ exome

AF:

0.360

Gnomad EAS exome

AF:

0.185

Gnomad SAS exome

AF:

0.281

Gnomad FIN exome

AF:

0.274

Gnomad NFE exome

AF:

0.349

Gnomad OTH exome

AF:

0.312

GnomAD4 exome

AF:

0.325

AC:

470573

AN:

1447328

Hom.:

78307

Cov.:

AF XY:

0.325

AC XY:

233727

AN XY:

718862

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.240

Gnomad4 ASJ exome

AF:

0.359

Gnomad4 EAS exome

AF:

0.214

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.272

Gnomad4 NFE exome

AF:

0.344

Gnomad4 OTH exome

AF:

0.307

GnomAD4 genome

AF:

0.266

AC:

40444

AN:

151922

Hom.:

6099

Cov.:

AF XY:

0.264

AC XY:

19568

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.358

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.285

Gnomad4 FIN

AF:

0.257

Gnomad4 NFE

AF:

0.347

Gnomad4 OTH

AF:

0.294

Alfa

AF:

0.313

Hom.:

1424

Bravo

AF:

0.260

Asia WGS

AF:

0.242

AC:

844

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.73

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over