rs2289311

Variant names:

• chr10-77805897-G-A
• rs2289311
• NM_004747.4:c.4968-36C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-77805897-G-A
• chr10-77805897-G-C
• chr10-77805897-G-T

Variant summary

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

The NM_004747.4(DLG5):​c.4968-36C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 1,575,354 control chromosomes in the GnomAD database, including 85,586 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 0.30 (7276 hom., cov: 32)
  • Exomes 𝑓: 0.33 (78310 hom.)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487
• Publications: 23 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG5	NM_004747.4	c.4968-36C>T		intron_variant	Intron 26 of 31	ENST00000372391.7	NP_004738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7	c.4968-36C>T		intron_variant	Intron 26 of 31	1	NM_004747.4	ENSP00000361467.2

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46267 AN: 151972 Hom.: 7276 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.327

GnomAD2 exomes AF: 0.302 AC: 69735 AN: 231068 AF XY: 0.306

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.244

Gnomad ASJ exome AF: 0.366

Gnomad EAS exome AF: 0.185

Gnomad FIN exome AF: 0.273

Gnomad NFE exome AF: 0.349

Gnomad OTH exome AF: 0.312

GnomAD4 exome AF: 0.329 AC: 468533 AN: 1423264 Hom.: 78310 Cov.: 28 AF XY: 0.328 AC XY: 230781 AN XY: 702916

African (AFR) AF: 0.271 AC: 8800 AN: 32482

American (AMR) AF: 0.245 AC: 10234 AN: 41830

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 8836 AN: 24572

East Asian (EAS) AF: 0.215 AC: 8382 AN: 39012

South Asian (SAS) AF: 0.282 AC: 23108 AN: 82008

European-Finnish (FIN) AF: 0.272 AC: 14292 AN: 52538

Middle Eastern (MID) AF: 0.322 AC: 1699 AN: 5274

European-Non Finnish (NFE) AF: 0.345 AC: 374612 AN: 1086948

Other (OTH) AF: 0.317 AC: 18570 AN: 58600

GnomAD4 genome AF: 0.304 AC: 46269 AN: 152090 Hom.: 7276 Cov.: 32 AF XY: 0.301 AC XY: 22385 AN XY: 74346

African (AFR) AF: 0.262 AC: 10865 AN: 41494

American (AMR) AF: 0.270 AC: 4120 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1244 AN: 3470

East Asian (EAS) AF: 0.188 AC: 970 AN: 5156

South Asian (SAS) AF: 0.288 AC: 1386 AN: 4818

European-Finnish (FIN) AF: 0.258 AC: 2734 AN: 10588

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23637 AN: 67974

Other (OTH) AF: 0.323 AC: 681 AN: 2106

Alfa AF: 0.278 Hom.: 2024

Bravo AF: 0.303

Asia WGS AF: 0.255 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.5
DANN	Benign	0.40
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs2289311; hg19: chr10-79565655; COSMIC: COSV64947886; COSMIC: COSV64947886;