rs1866435

chr10-77817175-G-Achr10-77817175-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004747.4(DLG5):c.3785-79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 1,307,428 control chromosomes in the GnomAD database, including 1,325 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 0.035 (152 hom., cov: 33)
  • Exomes 𝑓: 0.032 (1173 hom.)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG5	NM_004747.4	c.3785-79C>T		intron_variant		ENST00000372391.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG5	ENST00000372391.7	c.3785-79C>T		intron_variant		1	NM_004747.4	P1

Frequencies

GnomAD3 genomes AF: 0.0347 AC: 5273 AN: 152142 Hom.: 151 Cov.: 33

Gnomad AFR AF: 0.0314

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0835

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0234

Gnomad OTH AF: 0.0320

GnomAD4 exome AF: 0.0319 AC: 36862 AN: 1155166 Hom.: 1173 AF XY: 0.0323 AC XY: 19002 AN XY: 587824

Gnomad4 AFR exome AF: 0.0312

Gnomad4 AMR exome AF: 0.0381

Gnomad4 ASJ exome AF: 0.0789

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.0405

Gnomad4 FIN exome AF: 0.0294

Gnomad4 NFE exome AF: 0.0224

Gnomad4 OTH exome AF: 0.0425

GnomAD4 genome AF: 0.0347 AC: 5281 AN: 152262 Hom.: 152 Cov.: 33 AF XY: 0.0351 AC XY: 2610 AN XY: 74438

Gnomad4 AFR AF: 0.0313

Gnomad4 AMR AF: 0.0360

Gnomad4 ASJ AF: 0.0835

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.0537

Gnomad4 FIN AF: 0.0267

Gnomad4 NFE AF: 0.0234

Gnomad4 OTH AF: 0.0345

Alfa AF: 0.0152 Hom.: 11

Bravo AF: 0.0378

Asia WGS AF: 0.113 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.7
Dann	Benign	0.50

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: rs1866435; hg19: chr10-79576933;