10-77817175-G-A

Variant names:

• chr10-77817175-G-A
• rs1866435
• NM_004747.4:c.3785-79C>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.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
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004747.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG5	NM_004747.4	MANE Select	c.3785-79C>T		intron	N/A	NP_004738.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG5	ENST00000372391.7	TSL:1 MANE Select	c.3785-79C>T		intron	N/A	ENSP00000361467.2
	DLG5	ENST00000424842.5	TSL:1	c.668-79C>T		intron	N/A	ENSP00000394797.1
	DLG5	ENST00000459739.5	TSL:1	n.840-79C>T		intron	N/A

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

African (AFR) AF: 0.0312 AC: 860 AN: 27542

American (AMR) AF: 0.0381 AC: 1660 AN: 43618

Ashkenazi Jewish (ASJ) AF: 0.0789 AC: 1902 AN: 24100

East Asian (EAS) AF: 0.175 AC: 6645 AN: 38038

South Asian (SAS) AF: 0.0405 AC: 3235 AN: 79870

European-Finnish (FIN) AF: 0.0294 AC: 1546 AN: 52618

Middle Eastern (MID) AF: 0.0456 AC: 237 AN: 5200

European-Non Finnish (NFE) AF: 0.0224 AC: 18642 AN: 833968

Other (OTH) AF: 0.0425 AC: 2135 AN: 50212

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

African (AFR) AF: 0.0313 AC: 1300 AN: 41548

American (AMR) AF: 0.0360 AC: 550 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0835 AC: 290 AN: 3472

East Asian (EAS) AF: 0.176 AC: 913 AN: 5174

South Asian (SAS) AF: 0.0537 AC: 259 AN: 4822

European-Finnish (FIN) AF: 0.0267 AC: 283 AN: 10608

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0234 AC: 1591 AN: 68020

Other (OTH) AF: 0.0345 AC: 73 AN: 2116

Alfa AF: 0.0285 Hom.: 169

Bravo AF: 0.0378

Asia WGS AF: 0.113 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.50
PhyloP100		0.19
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: rs1866435; hg19: chr10-79576933;