Genetic Variant DLG4:c.210+40G>A (chr17-7203968-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001321075.3(DLG4):c.210+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00439 in 1,603,206 control chromosomes in the GnomAD database, including 274 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 0.022 ( 143 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 131 hom. )

Consequence

DLG4
NM_001321075.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.93

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NM_001321075.3 link	c.210+40G>A		intron_variant	Intron 4 of 19	ENST00000399506.9	NP_001308004.1	P78352-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DLG4	ENST00000399506.9 link	c.210+40G>A	intron_variant	Intron 4 of 19	2	NM_001321075.3	ENSP00000382425.2	P78352-1
DLG4	ENST00000648172.9 link	c.339+40G>A	intron_variant	Intron 6 of 21			ENSP00000497806.3	P78352-2
DLG4	ENST00000648896.1 link	c.309+40G>A	intron_variant	Intron 4 of 19			ENSP00000497546.1	A0A3B3ISQ5
DLG4	ENST00000649520.1 link	c.30+40G>A	intron_variant	Intron 3 of 18			ENSP00000497647.1	B7Z647
DLG4	ENST00000648263.1 link	c.30+40G>A	intron_variant	Intron 2 of 13			ENSP00000498035.1	A0A3B3IU19
DLG4	ENST00000647975.1 link	c.144+40G>A	intron_variant	Intron 3 of 6			ENSP00000497912.1	A0A3B3ITI9
DLG4	ENST00000451807.7 link	c.126+40G>A	intron_variant	Intron 3 of 7	5		ENSP00000407918.3	C9JYG3
DLG4	ENST00000648658.1 link	c.222+40G>A	intron_variant	Intron 4 of 5			ENSP00000496903.1	A0A3B3IRP2
DLG4	ENST00000648760.1 link	c.30+40G>A	intron_variant	Intron 3 of 3			ENSP00000497462.1	A0A3B3ISL1
DLG4	ENST00000650301.1 link	c.138+40G>A	intron_variant	Intron 3 of 3			ENSP00000497662.1	A0A3B3ITD1
DLG4	ENST00000491753.2 link	n.339+40G>A	intron_variant	Intron 6 of 20	2		ENSP00000467897.2	B7Z3U2

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3351

AN:

152068

Hom.:

143

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0764

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00943

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00594

AC:

1378

AN:

232128

AF XY:

0.00461

show subpopulations

Gnomad AFR exome

AF:

0.0841

Gnomad AMR exome

AF:

0.00484

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000382

Gnomad OTH exome

AF:

0.00316

GnomAD4 exome

AF:

0.00254

AC:

3681

AN:

1451020

Hom.:

131

Cov.:

AF XY:

0.00219

AC XY:

1576

AN XY:

720942

show subpopulations

African (AFR)

AF:

0.0855

AC:

2843

AN:

33240

American (AMR)

AF:

0.00552

AC:

237

AN:

42930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25848

East Asian (EAS)

AF:

0.00

AC:

AN:

39254

South Asian (SAS)

AF:

0.000142

AC:

AN:

84518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52764

Middle Eastern (MID)

AF:

0.00460

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.000206

AC:

228

AN:

1106830

Other (OTH)

AF:

0.00558

AC:

335

AN:

59984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

217

434

651

868

1085

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

200

300

400

500

<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:

0.0220

AC:

3354

AN:

152186

Hom.:

143

Cov.:

AF XY:

0.0211

AC XY:

1567

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.0763

AC:

3166

AN:

41494

American (AMR)

AF:

0.00942

AC:

144

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68006

Other (OTH)

AF:

0.00851

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

150

301

451

602

752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0113

Hom.:

Bravo

AF:

0.0256

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.50

(source)

DANN

Benign

0.56

PhyloP100

-1.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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