10-77818822-C-G

Variant names:

• chr10-77818822-C-G
• rs1248636
• NM_004747.4:c.3671+499G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004747.4(DLG5):​c.3671+499G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG5	NM_004747.4	c.3671+499G>C		intron_variant	Intron 17 of 31	ENST00000372391.7	NP_004738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7	c.3671+499G>C		intron_variant	Intron 17 of 31	1	NM_004747.4	ENSP00000361467.2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 288

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.061
DANN	Benign	0.35
PhyloP100		-0.77

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: rs1248636; hg19: chr10-79578580;