10-77856847-T-C

Variant names:

Variant summary

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

The NM_004747.4(DLG5):c.419A>G(p.Gln140Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 1,612,626 control chromosomes in the GnomAD database, including 666,809 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q140E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.93 ( 66442 hom., cov: 32)

Exomes 𝑓: 0.91 ( 600367 hom. )

Consequence

DLG5
NM_004747.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

85 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 (MetaRNN=9.029689E-7).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG5	NM_004747.4	MANE Select	c.419A>G	p.Gln140Arg	missense	Exon 3 of 32	NP_004738.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DLG5	ENST00000372391.7	TSL:1 MANE Select	c.419A>G	p.Gln140Arg	missense	Exon 3 of 32	ENSP00000361467.2
DLG5	ENST00000468332.6	TSL:2	n.194A>G		non_coding_transcript_exon	Exon 3 of 30	ENSP00000473298.1
DLG5	ENST00000475613.6	TSL:5	n.93+12252A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.933

AC:

141983

AN:

152128

Hom.:

66378

Cov.:

show subpopulations

Gnomad AFR

AF:

0.982

Gnomad AMI

AF:

0.955

Gnomad AMR

AF:

0.945

Gnomad ASJ

AF:

0.892

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.964

Gnomad FIN

AF:

0.925

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.897

Gnomad OTH

AF:

0.915

GnomAD2 exomes

AF:

0.930

AC:

232776

AN:

250204

AF XY:

0.928

show subpopulations

Gnomad AFR exome

AF:

0.984

Gnomad AMR exome

AF:

0.960

Gnomad ASJ exome

AF:

0.895

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.922

Gnomad NFE exome

AF:

0.898

Gnomad OTH exome

AF:

0.924

GnomAD4 exome

AF:

0.906

AC:

1323382

AN:

1460380

Hom.:

600367

Cov.:

AF XY:

0.907

AC XY:

658967

AN XY:

726472

show subpopulations

African (AFR)

AF:

0.984

AC:

32916

AN:

33438

American (AMR)

AF:

0.958

AC:

42842

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.894

AC:

23303

AN:

26056

East Asian (EAS)

AF:

1.00

AC:

39698

AN:

39700

South Asian (SAS)

AF:

0.963

AC:

82908

AN:

86094

European-Finnish (FIN)

AF:

0.919

AC:

49066

AN:

53400

Middle Eastern (MID)

AF:

0.943

AC:

4537

AN:

4810

European-Non Finnish (NFE)

AF:

0.893

AC:

992763

AN:

1111888

Other (OTH)

AF:

0.918

AC:

55349

AN:

60278

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

6943

13886

20828

27771

34714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21426

42852

64278

85704

107130

<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:

0.933

AC:

142106

AN:

152246

Hom.:

66442

Cov.:

AF XY:

0.936

AC XY:

69629

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.982

AC:

40816

AN:

41550

American (AMR)

AF:

0.945

AC:

14462

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.892

AC:

3098

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5166

AN:

5172

South Asian (SAS)

AF:

0.964

AC:

4640

AN:

4812

European-Finnish (FIN)

AF:

0.925

AC:

9812

AN:

10610

Middle Eastern (MID)

AF:

0.946

AC:

278

AN:

294

European-Non Finnish (NFE)

AF:

0.897

AC:

61027

AN:

68008

Other (OTH)

AF:

0.916

AC:

1938

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

497

994

1491

1988

2485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

912

1824

2736

3648

4560

<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:

0.912

Hom.:

211925

Bravo

AF:

0.936

TwinsUK

AF:

0.885

AC:

3280

ALSPAC

AF:

0.896

AC:

3455

ESP6500AA

AF:

0.983

AC:

4330

ESP6500EA

AF:

0.896

AC:

7708

ExAC

AF:

0.931

AC:

113000

Asia WGS

AF:

0.987

AC:

3433

AN:

3478

EpiCase

AF:

0.898

EpiControl

AF:

0.893

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.0

(source)

DANN

Benign

0.12

DEOGEN2

Benign

0.046

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.27

MetaRNN

Benign

9.0e-7

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.41

PhyloP100

1.1

PrimateAI

Benign

0.23

PROVEAN

Benign

0.76

REVEL

Benign

0.072

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.063

MPC

0.65

ClinPred

0.0023

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.029

gMVP

0.11

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over