rs1248653

Variant names:

• chr10-77866771-T-C
• rs1248653
• NM_004747.4:c.373+2358A>G

Variant summary

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

The NM_004747.4(DLG5):​c.373+2358A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 353,608 control chromosomes in the GnomAD database, including 14,230 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 (5473 hom., cov: 30)
  • Exomes 𝑓: 0.29 (8757 hom.)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327
• Publications: 3 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

ENSG00000204049 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG5	NM_004747.4	c.373+2358A>G		intron_variant	Intron 2 of 31	ENST00000372391.7	NP_004738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7	c.373+2358A>G		intron_variant	Intron 2 of 31	1	NM_004747.4	ENSP00000361467.2
DLG5	ENST00000468332.6	n.148+2358A>G		intron_variant	Intron 2 of 29	2		ENSP00000473298.1
DLG5	ENST00000475613.6	n.93+2328A>G		intron_variant	Intron 1 of 21	5
ENSG00000204049	ENST00000372387.2	n.-93T>C		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38507 AN: 151374 Hom.: 5465 Cov.: 30

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.176

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.237

GnomAD4 exome AF: 0.288 AC: 58197 AN: 202114 Hom.: 8757 AF XY: 0.289 AC XY: 32177 AN XY: 111180

African (AFR) AF: 0.152 AC: 802 AN: 5282

American (AMR) AF: 0.435 AC: 4950 AN: 11390

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 855 AN: 4494

East Asian (EAS) AF: 0.296 AC: 2433 AN: 8232

South Asian (SAS) AF: 0.308 AC: 13154 AN: 42712

European-Finnish (FIN) AF: 0.300 AC: 2625 AN: 8748

Middle Eastern (MID) AF: 0.193 AC: 210 AN: 1086

European-Non Finnish (NFE) AF: 0.276 AC: 30523 AN: 110472

Other (OTH) AF: 0.273 AC: 2645 AN: 9698

GnomAD4 genome AF: 0.254 AC: 38521 AN: 151494 Hom.: 5473 Cov.: 30 AF XY: 0.259 AC XY: 19189 AN XY: 73996

African (AFR) AF: 0.151 AC: 6236 AN: 41290

American (AMR) AF: 0.385 AC: 5861 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 615 AN: 3468

East Asian (EAS) AF: 0.306 AC: 1562 AN: 5112

South Asian (SAS) AF: 0.298 AC: 1424 AN: 4774

European-Finnish (FIN) AF: 0.311 AC: 3244 AN: 10444

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

European-Non Finnish (NFE) AF: 0.278 AC: 18856 AN: 67896

Other (OTH) AF: 0.235 AC: 492 AN: 2096

Alfa AF: 0.259 Hom.: 872

Bravo AF: 0.254

Asia WGS AF: 0.320 AC: 1117 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	0.46
DANN	Benign	0.55
PhyloP100		-0.33
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: rs1248653; hg19: chr10-79626529; COSMIC: COSV64946441; COSMIC: COSV64946441;