10-77791882-C-T

Variant names:

• chr10-77791882-C-T
• rs2165047
• NM_004747.4:c.*558G>A

Variant summary

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

The NM_004747.4(DLG5):​c.*558G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 154,080 control chromosomes in the GnomAD database, including 5,855 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 0.26 (5777 hom., cov: 33)
  • Exomes 𝑓: 0.27 (78 hom.)
• Consequence: DLG5 NM_004747.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.16
• Publications: 21 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):

• ciliopathy

  Inheritance: AD, AR Classification: LIMITED Submitted by: Franklin by Genoox
• Yuksel-Vogel-Bauer syndrome

  Inheritance: AD, AR Classification: LIMITED Submitted by: G2P
• congenital anomaly of kidney and urinary tract

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000228748 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.386 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG5	NM_004747.4	MANE Select	c.*558G>A		3_prime_UTR	Exon 32 of 32	NP_004738.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG5	ENST00000372391.7	TSL:1 MANE Select	c.*558G>A		3_prime_UTR	Exon 32 of 32	ENSP00000361467.2	Q8TDM6-1
	DLG5	ENST00000424842.5	TSL:1	c.*558G>A		3_prime_UTR	Exon 20 of 20	ENSP00000394797.1	A0A0A0MSL1
	ENSG00000228748	ENST00000434097.2	TSL:1	n.734C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39983 AN: 152026 Hom.: 5766 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.267

GnomAD4 exome AF: 0.267 AC: 517 AN: 1936 Hom.: 78 Cov.: 0 AF XY: 0.268 AC XY: 273 AN XY: 1018

African (AFR) AF: 0.152 AC: 7 AN: 46

American (AMR) AF: 0.275 AC: 11 AN: 40

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 7 AN: 34

East Asian (EAS) AF: 0.346 AC: 36 AN: 104

South Asian (SAS) AF: 0.250 AC: 5 AN: 20

European-Finnish (FIN) AF: 0.312 AC: 176 AN: 564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.249 AC: 261 AN: 1048

Other (OTH) AF: 0.179 AC: 14 AN: 78

GnomAD4 genome AF: 0.263 AC: 40020 AN: 152144 Hom.: 5777 Cov.: 33 AF XY: 0.268 AC XY: 19930 AN XY: 74382

African (AFR) AF: 0.171 AC: 7102 AN: 41512

American (AMR) AF: 0.395 AC: 6033 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 654 AN: 3472

East Asian (EAS) AF: 0.298 AC: 1546 AN: 5180

South Asian (SAS) AF: 0.302 AC: 1455 AN: 4820

European-Finnish (FIN) AF: 0.310 AC: 3275 AN: 10576

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19142 AN: 67984

Other (OTH) AF: 0.265 AC: 560 AN: 2110

Alfa AF: 0.267 Hom.: 7247

Bravo AF: 0.265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.076
DANN	Benign	0.50
PhyloP100		-4.2
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: rs2165047; hg19: chr10-79551640; COSMIC: COSV64947657; COSMIC: COSV64947657;