17-7206676-A-G

Variant names:

• chr17-7206676-A-G
• rs390200
• NM_001321075.3:c.96+1498T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321075.3(DLG4):​c.96+1498T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,884 control chromosomes in the GnomAD database, including 23,532 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 0.55 (23532 hom., cov: 31)
• Consequence: DLG4 NM_001321075.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• Publications: 32 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NM_001321075.3	c.96+1498T>C		intron_variant	Intron 2 of 19	ENST00000399506.9	NP_001308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000399506.9	c.96+1498T>C		intron_variant	Intron 2 of 19	2	NM_001321075.3	ENSP00000382425.2
DLG4	ENST00000648172.9	c.225+1498T>C		intron_variant	Intron 4 of 21			ENSP00000497806.3
DLG4	ENST00000648896.1	c.195+1399T>C		intron_variant	Intron 2 of 19			ENSP00000497546.1
DLG4	ENST00000647975.1	c.31-2424T>C		intron_variant	Intron 1 of 6			ENSP00000497912.1
DLG4	ENST00000648658.1	c.108+1498T>C		intron_variant	Intron 2 of 5			ENSP00000496903.1
DLG4	ENST00000648760.1	c.-85+1498T>C		intron_variant	Intron 1 of 3			ENSP00000497462.1
DLG4	ENST00000650301.1	c.24+255T>C		intron_variant	Intron 1 of 3			ENSP00000497662.1
DLG4	ENST00000491753.2	n.225+1498T>C		intron_variant	Intron 4 of 20	2		ENSP00000467897.2

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83092 AN: 151768 Hom.: 23515 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.570

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.547 AC: 83141 AN: 151884 Hom.: 23532 Cov.: 31 AF XY: 0.552 AC XY: 40974 AN XY: 74248

African (AFR) AF: 0.412 AC: 17059 AN: 41374

American (AMR) AF: 0.512 AC: 7807 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2032 AN: 3470

East Asian (EAS) AF: 0.470 AC: 2431 AN: 5168

South Asian (SAS) AF: 0.630 AC: 3034 AN: 4818

European-Finnish (FIN) AF: 0.675 AC: 7135 AN: 10564

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.614 AC: 41702 AN: 67930

Other (OTH) AF: 0.575 AC: 1210 AN: 2104

Alfa AF: 0.588 Hom.: 80806

Bravo AF: 0.524

Asia WGS AF: 0.561 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.6
DANN	Benign	0.80
PhyloP100		-0.48
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

Other links and lift over

dbSNP: rs390200; hg19: chr17-7109995;