rs11002306

chr10-77831761-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DLG5	NM_004747.4	c.1749-888T>A		intron_variant		ENST00000372391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG5	ENST00000372391.7	c.1749-888T>A		intron_variant		1	NM_004747.4	P1
DLG5	ENST00000468332.6	c.*1106-888T>A		intron_variant, NMD_transcript_variant		2
DLG5	ENST00000475613.6	n.94-888T>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.258

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.305

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

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

LitVar

Other links and lift over

dbSNP: rs11002306; hg19: chr10-79591519;