dbSNP rs1248674: DLG5:c.865-1632T>G (chr10-77845338-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004747.4(DLG5):c.865-1632T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,108 control chromosomes in the GnomAD database, including 44,101 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 0.75 ( 44093 hom., cov: 32)

Exomes 𝑓: 0.86 ( 8 hom. )

Consequence

DLG5
NM_004747.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0310

Publications

2 publications found

Variant links:

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

DLG5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG5	NM_004747.4 link	c.865-1632T>G		intron_variant	Intron 5 of 31	ENST00000372391.7	NP_004738.3	Q8TDM6-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DLG5	ENST00000372391.7 link	c.865-1632T>G	intron_variant	Intron 5 of 31	1	NM_004747.4	ENSP00000361467.2	Q8TDM6-1
DLG5	ENST00000468332.6 link	n.*94T>G	non_coding_transcript_exon_variant	Exon 6 of 30	2		ENSP00000473298.1	R4GMQ2
DLG5	ENST00000468332.6 link	n.*94T>G	3_prime_UTR_variant	Exon 6 of 30	2		ENSP00000473298.1	R4GMQ2
DLG5	ENST00000475613.6 link	n.94-14465T>G	intron_variant	Intron 1 of 21	5

Frequencies

GnomAD3 genomes

AF:

0.751

AC:

114130

AN:

151968

Hom.:

44029

Cov.:

show subpopulations

Gnomad AFR

AF:

0.937

Gnomad AMI

AF:

0.805

Gnomad AMR

AF:

0.770

Gnomad ASJ

AF:

0.689

Gnomad EAS

AF:

0.748

Gnomad SAS

AF:

0.673

Gnomad FIN

AF:

0.610

Gnomad MID

AF:

0.704

Gnomad NFE

AF:

0.665

Gnomad OTH

AF:

0.729

GnomAD4 exome

AF:

0.864

AC:

AN:

Hom.:

Cov.:

AF XY:

0.889

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.813

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.751

AC:

114253

AN:

152086

Hom.:

44093

Cov.:

AF XY:

0.747

AC XY:

55527

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.937

AC:

38933

AN:

41546

American (AMR)

AF:

0.770

AC:

11777

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.689

AC:

2389

AN:

3468

East Asian (EAS)

AF:

0.747

AC:

3838

AN:

5138

South Asian (SAS)

AF:

0.674

AC:

3243

AN:

4814

European-Finnish (FIN)

AF:

0.610

AC:

6433

AN:

10552

Middle Eastern (MID)

AF:

0.688

AC:

201

AN:

292

European-Non Finnish (NFE)

AF:

0.665

AC:

45167

AN:

67962

Other (OTH)

AF:

0.730

AC:

1538

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1347

2695

4042

5390

6737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.719

Hom.:

5255

Bravo

AF:

0.773

Asia WGS

AF:

0.770

AC:

2680

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.79

(source)

DANN

Benign

0.43

PhyloP100

-0.031

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over