rs1268956

Variant names:

• chr10-77848519-C-T
• rs1268956
• NM_004747.4:c.865-4813G>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.865-4813G>A 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 151,984 control chromosomes in the GnomAD database, including 5,480 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 (5480 hom., cov: 32)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.858
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG5	NM_004747.4	c.865-4813G>A		intron_variant	Intron 5 of 31	ENST00000372391.7	NP_004738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7	c.865-4813G>A		intron_variant	Intron 5 of 31	1	NM_004747.4	ENSP00000361467.2
DLG5	ENST00000468332.6	n.640-3082G>A		intron_variant	Intron 5 of 29	2		ENSP00000473298.1
DLG5	ENST00000475613.6	n.94-17646G>A		intron_variant	Intron 1 of 21	5

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38627 AN: 151866 Hom.: 5472 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.176

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: 38641 AN: 151984 Hom.: 5480 Cov.: 32 AF XY: 0.259 AC XY: 19271 AN XY: 74292

African (AFR) AF: 0.151 AC: 6251 AN: 41462

American (AMR) AF: 0.387 AC: 5907 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 616 AN: 3472

East Asian (EAS) AF: 0.308 AC: 1589 AN: 5160

South Asian (SAS) AF: 0.299 AC: 1438 AN: 4808

European-Finnish (FIN) AF: 0.309 AC: 3259 AN: 10552

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.277 AC: 18850 AN: 67938

Other (OTH) AF: 0.237 AC: 500 AN: 2112

Alfa AF: 0.275 Hom.: 1516

Bravo AF: 0.254

Asia WGS AF: 0.320 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.31
PhyloP100		-0.86
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: rs1268956; hg19: chr10-79608277;