rs11002306

Variant names:

• chr10-77831761-A-T
• rs11002306
• NM_004747.4:c.1749-888T>A

Variant summary

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

The NM_004747.4(DLG5):​c.1749-888T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,200 control chromosomes in the GnomAD database, including 6,638 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 0.29 (6638 hom., cov: 33)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 6 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG5	NM_004747.4	c.1749-888T>A		intron_variant	Intron 9 of 31	ENST00000372391.7	NP_004738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7	c.1749-888T>A		intron_variant	Intron 9 of 31	1	NM_004747.4	ENSP00000361467.2
DLG5	ENST00000468332.6	n.*1106-888T>A		intron_variant	Intron 10 of 29	2		ENSP00000473298.1
DLG5	ENST00000475613.6	n.94-888T>A		intron_variant	Intron 1 of 21	5

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43716 AN: 152082 Hom.: 6643 Cov.: 33

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.308

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.287 AC: 43710 AN: 152200 Hom.: 6638 Cov.: 33 AF XY: 0.283 AC XY: 21071 AN XY: 74404

African (AFR) AF: 0.208 AC: 8623 AN: 41538

American (AMR) AF: 0.262 AC: 4008 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1264 AN: 3472

East Asian (EAS) AF: 0.188 AC: 975 AN: 5180

South Asian (SAS) AF: 0.283 AC: 1364 AN: 4824

European-Finnish (FIN) AF: 0.258 AC: 2731 AN: 10596

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23456 AN: 67988

Other (OTH) AF: 0.305 AC: 642 AN: 2108

Alfa AF: 0.309 Hom.: 915

Bravo AF: 0.284

Asia WGS AF: 0.245 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.38
DANN	Benign	0.45
PhyloP100		-1.1
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

Other links and lift over

dbSNP: rs11002306; hg19: chr10-79591519;