rs2289308

Variant names:

• chr10-77819493-G-A
• rs2289308
• NM_004747.4:c.3527-28C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 14 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DLG5	NM_004747.4	c.3527-28C>T		intron_variant	Intron 16 of 31	ENST00000372391.7	NP_004738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7	c.3527-28C>T		intron_variant	Intron 16 of 31	1	NM_004747.4	ENSP00000361467.2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40461 AN: 151804 Hom.: 6101 Cov.: 31

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

GnomAD2 exomes AF: 0.292 AC: 69339 AN: 237826 AF XY: 0.298

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 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.: 38 AF XY: 0.325 AC XY: 233727 AN XY: 718862

African (AFR) AF: 0.126 AC: 4171 AN: 33084

American (AMR) AF: 0.240 AC: 10399 AN: 43372

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 9039 AN: 25166

East Asian (EAS) AF: 0.214 AC: 8462 AN: 39528

South Asian (SAS) AF: 0.282 AC: 23789 AN: 84344

European-Finnish (FIN) AF: 0.272 AC: 14330 AN: 52630

Middle Eastern (MID) AF: 0.318 AC: 1370 AN: 4306

European-Non Finnish (NFE) AF: 0.344 AC: 380695 AN: 1105304

Other (OTH) AF: 0.307 AC: 18318 AN: 59594

GnomAD4 genome AF: 0.266 AC: 40444 AN: 151922 Hom.: 6099 Cov.: 31 AF XY: 0.264 AC XY: 19568 AN XY: 74250

African (AFR) AF: 0.131 AC: 5418 AN: 41422

American (AMR) AF: 0.256 AC: 3916 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1240 AN: 3464

East Asian (EAS) AF: 0.188 AC: 968 AN: 5156

South Asian (SAS) AF: 0.285 AC: 1374 AN: 4816

European-Finnish (FIN) AF: 0.257 AC: 2712 AN: 10548

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.347 AC: 23566 AN: 67922

Other (OTH) AF: 0.294 AC: 620 AN: 2110

Alfa AF: 0.317 Hom.: 2567

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
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2289308; hg19: chr10-79579251; COSMIC: COSV64948244; COSMIC: COSV64948244;