rs1650146

Positions:

• chr10-77928450-A-G
• chr10-77928450-A-T

Variant summary

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

The XM_047425998.1(DLG5):​c.-27+12220T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,202 control chromosomes in the GnomAD database, including 40,737 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 0.72 (40721 hom., cov: 32)
  • Exomes 𝑓: 0.66 (16 hom.)
• Consequence: DLG5 XM_047425998.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.856

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-AS1 (HGNC:45109): (DLG5 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG5	XM_047425998.1	c.-27+12220T>C		intron_variant			XP_047281954.1
DLG5-AS1	NR_024585.1	n.1639A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG5-AS1	ENST00000632919.1	n.820A>G		non_coding_transcript_exon_variant	1/1	6
DLG5-AS1	ENST00000449852.1	n.251+828A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109201 AN: 152020 Hom.: 40659 Cov.: 32

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.694

GnomAD4 exome AF: 0.656 AC: 42 AN: 64 Hom.: 16 Cov.: 0 AF XY: 0.646 AC XY: 31 AN XY: 48

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.750

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.640

GnomAD4 genome AF: 0.719 AC: 109324 AN: 152138 Hom.: 40721 Cov.: 32 AF XY: 0.715 AC XY: 53175 AN XY: 74356

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.734

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.772

Gnomad4 SAS AF: 0.650

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.695

Alfa AF: 0.675 Hom.: 8597

Bravo AF: 0.740

Asia WGS AF: 0.764 AC: 2658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.2
DANN	Benign	0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1650146; hg19: chr10-79688208;