Genetic Variant DLG4:p.Ser674Ser (chr17-7191976-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001321075.3(DLG4):c.1893G>A(p.Ser631Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000637 in 1,461,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

DLG4
NM_001321075.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.50

Publications

1 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

DLG4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 17-7191976-C-T is Benign according to our data. Variant chr17-7191976-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 745399.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321075.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DLG4	NM_001365.5	MANE Plus Clinical	c.2022G>A	p.Ser674Ser	synonymous	Exon 20 of 22	NP_001356.1	P78352-2
DLG4	NM_001321075.3	MANE Select	c.1893G>A	p.Ser631Ser	synonymous	Exon 18 of 20	NP_001308004.1	P78352-1
DLG4	NM_001321074.1		c.2013G>A	p.Ser671Ser	synonymous	Exon 20 of 22	NP_001308003.1	B9EGL1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DLG4	ENST00000648172.9	MANE Plus Clinical	c.2022G>A	p.Ser674Ser	synonymous	Exon 20 of 22	ENSP00000497806.3	P78352-2
DLG4	ENST00000399506.9	TSL:2 MANE Select	c.1893G>A	p.Ser631Ser	synonymous	Exon 18 of 20	ENSP00000382425.2	P78352-1
DLG4	ENST00000399510.8	TSL:1	c.2013G>A	p.Ser671Ser	synonymous	Exon 20 of 22	ENSP00000382428.3	B9EGL1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000174

AC:

AN:

143908

AF XY:

0.000191

show subpopulations

Gnomad AFR exome

AF:

0.000281

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000649

AC:

AN:

1308924

Hom.:

Cov.:

AF XY:

0.0000810

AC XY:

AN XY:

641716

show subpopulations

African (AFR)

AF:

0.0000725

AC:

AN:

27598

American (AMR)

AF:

0.00

AC:

AN:

25062

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18896

East Asian (EAS)

AF:

0.00

AC:

AN:

33608

South Asian (SAS)

AF:

0.00121

AC:

AN:

62112

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48224

Middle Eastern (MID)

AF:

0.000588

AC:

AN:

5102

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1035088

Other (OTH)

AF:

0.0000939

AC:

AN:

53234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000526

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41484

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00104

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000580

Hom.:

Bravo

AF:

0.0000227

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

DLG4-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

-2.5

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.25

Position offset: -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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over