dbSNP rs1248634: DLG5:p.Gly1176Gly (chr10-77819464-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_004747.4(DLG5):c.3528C>T(p.Gly1176Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 1,612,028 control chromosomes in the GnomAD database, including 66,437 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5320 hom., cov: 32)

Exomes 𝑓: 0.29 ( 61117 hom. )

Consequence

DLG5
NM_004747.4 splice_region, synonymous

Scores

Splicing: ADA: 0.0003867

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.319

Publications

23 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP7

Synonymous conserved (PhyloP=0.319 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG5	NM_004747.4 link	c.3528C>T	p.Gly1176Gly	splice_region_variant, synonymous_variant	Exon 17 of 32	ENST00000372391.7	NP_004738.3	Q8TDM6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG5	ENST00000372391.7 link	c.3528C>T	p.Gly1176Gly	splice_region_variant, synonymous_variant	Exon 17 of 32	1	NM_004747.4	ENSP00000361467.2		Q8TDM6-1

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37623

AN:

151934

Hom.:

5313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.301

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.246

GnomAD2 exomes

AF:

0.293

AC:

73059

AN:

248956

AF XY:

0.290

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.193

Gnomad EAS exome

AF:

0.291

Gnomad FIN exome

AF:

0.295

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.285

AC:

416779

AN:

1459978

Hom.:

61117

Cov.:

AF XY:

0.284

AC XY:

206448

AN XY:

726274

show subpopulations

African (AFR)

AF:

0.121

AC:

4053

AN:

33444

American (AMR)

AF:

0.457

AC:

20363

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

4845

AN:

26032

East Asian (EAS)

AF:

0.316

AC:

12543

AN:

39688

South Asian (SAS)

AF:

0.309

AC:

26639

AN:

86114

European-Finnish (FIN)

AF:

0.294

AC:

15652

AN:

53314

Middle Eastern (MID)

AF:

0.200

AC:

1011

AN:

5058

European-Non Finnish (NFE)

AF:

0.284

AC:

315168

AN:

1111480

Other (OTH)

AF:

0.274

AC:

16505

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

15877

31754

47631

63508

79385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10662

21324

31986

42648

53310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.248

AC:

37642

AN:

152050

Hom.:

5320

Cov.:

AF XY:

0.253

AC XY:

18783

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.129

AC:

5367

AN:

41518

American (AMR)

AF:

0.383

AC:

5852

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

628

AN:

3468

East Asian (EAS)

AF:

0.300

AC:

1543

AN:

5140

South Asian (SAS)

AF:

0.298

AC:

1433

AN:

4808

European-Finnish (FIN)

AF:

0.310

AC:

3272

AN:

10562

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.276

AC:

18781

AN:

67980

Other (OTH)

AF:

0.245

AC:

515

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1416

2832

4247

5663

7079

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<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:

0.266

Hom.:

19560

Bravo

AF:

0.247

Asia WGS

AF:

0.309

AC:

1078

AN:

3478

EpiCase

AF:

0.259

EpiControl

AF:

0.259

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=35/65

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00039

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over