Genetic Variant DLG4:n.48G>A (chr17-7192188-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000489885.1(DLG4):n.48G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 435,494 control chromosomes in the GnomAD database, including 36,753 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 0.39 ( 11612 hom., cov: 29)

Exomes 𝑓: 0.42 ( 25141 hom. )

Consequence

DLG4
ENST00000489885.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0220

Publications

14 publications found

Variant links:

Genes affected

DLG4 (HGNC:2903): (discs large MAGUK scaffold protein 4) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. It heteromultimerizes with another MAGUK protein, DLG2, and is recruited into NMDA receptor and potassium channel clusters. These two MAGUK proteins may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DLG4 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
intellectual developmental disorder 62
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

DLG4 links:

ENSG00000279812 (HGNC:):

ENSG00000279812 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NM_001365.5 link	c.1996-186G>A		intron_variant	Intron 19 of 21	ENST00000648172.9	NP_001356.1
DLG4	NM_001321075.3 link	c.1867-186G>A		intron_variant	Intron 17 of 19	ENST00000399506.9	NP_001308004.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
DLG4	ENST00000648172.9 link	c.1996-186G>A	intron_variant	Intron 19 of 21		NM_001365.5	ENSP00000497806.3
DLG4	ENST00000399506.9 link	c.1867-186G>A	intron_variant	Intron 17 of 19	2	NM_001321075.3	ENSP00000382425.2
DLG4	ENST00000648896.1 link	c.1966-186G>A	intron_variant	Intron 17 of 19			ENSP00000497546.1
DLG4	ENST00000649520.1 link	c.1687-186G>A	intron_variant	Intron 16 of 18			ENSP00000497647.1
DLG4	ENST00000491753.2 link	n.1995+757G>A	intron_variant	Intron 19 of 20	2		ENSP00000467897.2

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58260

AN:

151186

Hom.:

11595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.396

Gnomad ASJ

AF:

0.394

Gnomad EAS

AF:

0.408

Gnomad SAS

AF:

0.382

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.551

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.402

GnomAD4 exome

AF:

0.417

AC:

118431

AN:

284190

Hom.:

25141

Cov.:

AF XY:

0.419

AC XY:

61487

AN XY:

146838

show subpopulations

African (AFR)

AF:

0.276

AC:

2092

AN:

7584

American (AMR)

AF:

0.347

AC:

3251

AN:

9364

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

3920

AN:

9810

East Asian (EAS)

AF:

0.391

AC:

9089

AN:

23252

South Asian (SAS)

AF:

0.363

AC:

4276

AN:

11790

European-Finnish (FIN)

AF:

0.411

AC:

9533

AN:

23216

Middle Eastern (MID)

AF:

0.520

AC:

766

AN:

1474

European-Non Finnish (NFE)

AF:

0.435

AC:

78023

AN:

179412

Other (OTH)

AF:

0.409

AC:

7481

AN:

18288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

3286

6572

9858

13144

16430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.385

AC:

58313

AN:

151304

Hom.:

11612

Cov.:

AF XY:

0.385

AC XY:

28431

AN XY:

73898

show subpopulations

African (AFR)

AF:

0.292

AC:

12036

AN:

41208

American (AMR)

AF:

0.396

AC:

6007

AN:

15180

Ashkenazi Jewish (ASJ)

AF:

0.394

AC:

1365

AN:

3468

East Asian (EAS)

AF:

0.407

AC:

2073

AN:

5094

South Asian (SAS)

AF:

0.384

AC:

1839

AN:

4786

European-Finnish (FIN)

AF:

0.414

AC:

4339

AN:

10488

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.433

AC:

29324

AN:

67764

Other (OTH)

AF:

0.407

AC:

861

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1710

3420

5129

6839

8549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<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:

0.403

Hom.:

7995

Bravo

AF:

0.377

Asia WGS

AF:

0.416

AC:

1447

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

-0.022

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.95

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over