chr17-7196492-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001321075.3(DLG4):c.1167C>T(p.Ile389Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,613,368 control chromosomes in the GnomAD database, including 77,375 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6382 hom., cov: 32)

Exomes 𝑓: 0.31 ( 70993 hom. )

Consequence

DLG4
NM_001321075.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.74

Publications

50 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 17-7196492-G-A is Benign according to our data. Variant chr17-7196492-G-A is described in ClinVar as Benign. ClinVar VariationId is 1255506.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NM_001321075.3 link	c.1167C>T	p.Ile389Ile	synonymous_variant	Exon 10 of 20	ENST00000399506.9	NP_001308004.1	P78352-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DLG4	ENST00000399506.9 link	c.1167C>T	p.Ile389Ile	synonymous_variant	Exon 10 of 20	2	NM_001321075.3	ENSP00000382425.2	P78352-1
DLG4	ENST00000648172.9 link	c.1296C>T	p.Ile432Ile	synonymous_variant	Exon 12 of 22			ENSP00000497806.3	P78352-2
DLG4	ENST00000648896.1 link	c.1266C>T	p.Ile422Ile	synonymous_variant	Exon 10 of 20			ENSP00000497546.1	A0A3B3ISQ5
DLG4	ENST00000649520.1 link	c.987C>T	p.Ile329Ile	synonymous_variant	Exon 9 of 19			ENSP00000497647.1	B7Z647
DLG4	ENST00000648263.1 link	c.987C>T	p.Ile329Ile	synonymous_variant	Exon 8 of 14			ENSP00000498035.1	A0A3B3IU19
DLG4	ENST00000491753.2 link	n.1296C>T		non_coding_transcript_exon_variant	Exon 12 of 21	2		ENSP00000467897.2	B7Z3U2

Frequencies

GnomAD3 genomes

AF:

0.281

AC:

42701

AN:

151992

Hom.:

6380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.239

Gnomad ASJ

AF:

0.305

Gnomad EAS

AF:

0.311

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.326

Gnomad OTH

AF:

0.300

GnomAD2 exomes

AF:

0.283

AC:

70531

AN:

249188

AF XY:

0.286

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.307

Gnomad EAS exome

AF:

0.312

Gnomad FIN exome

AF:

0.402

Gnomad NFE exome

AF:

0.326

Gnomad OTH exome

AF:

0.300

GnomAD4 exome

AF:

0.307

AC:

449018

AN:

1461258

Hom.:

70993

Cov.:

AF XY:

0.306

AC XY:

222099

AN XY:

726908

show subpopulations

African (AFR)

AF:

0.193

AC:

6470

AN:

33476

American (AMR)

AF:

0.161

AC:

7213

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

8085

AN:

26130

East Asian (EAS)

AF:

0.289

AC:

11479

AN:

39696

South Asian (SAS)

AF:

0.201

AC:

17371

AN:

86250

European-Finnish (FIN)

AF:

0.394

AC:

21056

AN:

53390

Middle Eastern (MID)

AF:

0.309

AC:

1780

AN:

5766

European-Non Finnish (NFE)

AF:

0.322

AC:

357400

AN:

1111460

Other (OTH)

AF:

0.301

AC:

18164

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

17736

35472

53209

70945

88681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11390

22780

34170

45560

56950

<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:

0.281

AC:

42707

AN:

152110

Hom.:

6382

Cov.:

AF XY:

0.281

AC XY:

20898

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.197

AC:

8181

AN:

41516

American (AMR)

AF:

0.239

AC:

3654

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.305

AC:

1060

AN:

3470

East Asian (EAS)

AF:

0.310

AC:

1603

AN:

5166

South Asian (SAS)

AF:

0.191

AC:

921

AN:

4822

European-Finnish (FIN)

AF:

0.394

AC:

4166

AN:

10570

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.326

AC:

22134

AN:

67968

Other (OTH)

AF:

0.296

AC:

626

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1575

3150

4724

6299

7874

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

426

852

1278

1704

2130

<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:

0.304

Hom.:

27526

Bravo

AF:

0.264

Asia WGS

AF:

0.211

AC:

735

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 03, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Intellectual developmental disorder 62

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

DLG4-related disorder

Benign:1

Sep 24, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

9.3

(source)

DANN

Benign

0.80

PhyloP100

-2.7

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over