rs1270912

Variant names:

• chr10-77838130-A-G
• rs1270912
• NM_004747.4:c.1438-2208T>C

Variant summary

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

The NM_004747.4(DLG5):​c.1438-2208T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.729 in 152,134 control chromosomes in the GnomAD database, including 41,186 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 0.73 (41186 hom., cov: 33)
• Consequence: DLG5 NM_004747.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 4 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG5	NM_004747.4	c.1438-2208T>C		intron_variant	Intron 7 of 31	ENST00000372391.7	NP_004738.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7	c.1438-2208T>C		intron_variant	Intron 7 of 31	1	NM_004747.4	ENSP00000361467.2
DLG5	ENST00000468332.6	n.*795-2208T>C		intron_variant	Intron 8 of 29	2		ENSP00000473298.1
DLG5	ENST00000475613.6	n.94-7257T>C		intron_variant	Intron 1 of 21	5

Frequencies

GnomAD3 genomes AF: 0.729 AC: 110868 AN: 152016 Hom.: 41140 Cov.: 33

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.729 AC: 110972 AN: 152134 Hom.: 41186 Cov.: 33 AF XY: 0.726 AC XY: 54000 AN XY: 74356

African (AFR) AF: 0.866 AC: 35986 AN: 41534

American (AMR) AF: 0.757 AC: 11571 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2358 AN: 3472

East Asian (EAS) AF: 0.737 AC: 3791 AN: 5144

South Asian (SAS) AF: 0.672 AC: 3242 AN: 4822

European-Finnish (FIN) AF: 0.611 AC: 6456 AN: 10572

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45143 AN: 67994

Other (OTH) AF: 0.709 AC: 1495 AN: 2108

Alfa AF: 0.708 Hom.: 6129

Bravo AF: 0.747

Asia WGS AF: 0.766 AC: 2663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.62
DANN	Benign	0.85
PhyloP100		-1.2
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: rs1270912; hg19: chr10-79597888;