17-7203968-C-T

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

2

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

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
DLG4NM_001321075.3 linkc.210+40G>A intron_variant Intron 4 of 19 ENST00000399506.9 NP_001308004.1 P78352-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DLG4ENST00000399506.9 linkc.210+40G>A intron_variant Intron 4 of 19 2 NM_001321075.3 ENSP00000382425.2 P78352-1
DLG4ENST00000648172.9 linkc.339+40G>A intron_variant Intron 6 of 21 ENSP00000497806.3 P78352-2
DLG4ENST00000648896.1 linkc.309+40G>A intron_variant Intron 4 of 19 ENSP00000497546.1 A0A3B3ISQ5
DLG4ENST00000649520.1 linkc.30+40G>A intron_variant Intron 3 of 18 ENSP00000497647.1 B7Z647
DLG4ENST00000648263.1 linkc.30+40G>A intron_variant Intron 2 of 13 ENSP00000498035.1 A0A3B3IU19
DLG4ENST00000647975.1 linkc.144+40G>A intron_variant Intron 3 of 6 ENSP00000497912.1 A0A3B3ITI9
DLG4ENST00000451807.7 linkc.126+40G>A intron_variant Intron 3 of 7 5 ENSP00000407918.3 C9JYG3
DLG4ENST00000648658.1 linkc.222+40G>A intron_variant Intron 4 of 5 ENSP00000496903.1 A0A3B3IRP2
DLG4ENST00000648760.1 linkc.30+40G>A intron_variant Intron 3 of 3 ENSP00000497462.1 A0A3B3ISL1
DLG4ENST00000650301.1 linkc.138+40G>A intron_variant Intron 3 of 3 ENSP00000497662.1 A0A3B3ITD1
DLG4ENST00000491753.2 linkn.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.:
32
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.:
32
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:
0
AN:
25848
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39254
South Asian (SAS)
AF:
0.000142
AC:
12
AN:
84518
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52764
Middle Eastern (MID)
AF:
0.00460
AC:
26
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
0
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
0
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.:
32
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:
1
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5172
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4816
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
0.00680
AC:
2
AN:
294
European-Non Finnish (NFE)
AF:
0.000338
AC:
23
AN:
68006
Other (OTH)
AF:
0.00851
AC:
18
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
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
0
34
68
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.:
21
Bravo
AF:
0.0256
Asia WGS
AF:
0.00433
AC:
16
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
DANN
Benign
0.56
PhyloP100
-1.9
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs373339; hg19: chr17-7107287; API