Genetic Variant NM_001321075.3:c.210+40G>T (chr17-7203968-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001321075.3(DLG4):c.210+40G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,451,024 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000431

AC:

AN:

232128

AF XY:

0.00000796

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000308

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:

6.89e-7

AC:

AN:

1451024

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720944

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33240

American (AMR)

AF:

0.0000233

AC:

AN:

42930

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25848

East Asian (EAS)

AF:

0.00

AC:

AN:

39254

South Asian (SAS)

AF:

0.00

AC:

AN:

84518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52764

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106834

Other (OTH)

AF:

0.00

AC:

AN:

59984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.14

(source)

DANN

Benign

0.58

PhyloP100

-1.9

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over