ENST00000489885.1:n.48G>A

Variant names:

• chr17-7192188-C-T
• rs2242449
• ENST00000489885.1:n.48G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000489885.1(DLG4):​n.48G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 435,494 control chromosomes in the GnomAD database, including 36,753 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 0.39 (11612 hom., cov: 29)
  • Exomes 𝑓: 0.42 (25141 hom.)
• Consequence: DLG4 ENST00000489885.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220
• Publications: 14 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

ENSG00000279812 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000489885.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG4	NM_001365.5	MANE Plus Clinical	c.1996-186G>A		intron	N/A	NP_001356.1
	DLG4	NM_001321075.3	MANE Select	c.1867-186G>A		intron	N/A	NP_001308004.1
	DLG4	NM_001321074.1		c.1987-186G>A		intron	N/A	NP_001308003.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG4	ENST00000489885.1	TSL:1	n.48G>A		non_coding_transcript_exon	Exon 1 of 2
	DLG4	ENST00000648172.9	MANE Plus Clinical	c.1996-186G>A		intron	N/A	ENSP00000497806.3
	DLG4	ENST00000399506.9	TSL:2 MANE Select	c.1867-186G>A		intron	N/A	ENSP00000382425.2

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58260 AN: 151186 Hom.: 11595 Cov.: 29

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.402

GnomAD4 exome AF: 0.417 AC: 118431 AN: 284190 Hom.: 25141 Cov.: 2 AF XY: 0.419 AC XY: 61487 AN XY: 146838

African (AFR) AF: 0.276 AC: 2092 AN: 7584

American (AMR) AF: 0.347 AC: 3251 AN: 9364

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 3920 AN: 9810

East Asian (EAS) AF: 0.391 AC: 9089 AN: 23252

South Asian (SAS) AF: 0.363 AC: 4276 AN: 11790

European-Finnish (FIN) AF: 0.411 AC: 9533 AN: 23216

Middle Eastern (MID) AF: 0.520 AC: 766 AN: 1474

European-Non Finnish (NFE) AF: 0.435 AC: 78023 AN: 179412

Other (OTH) AF: 0.409 AC: 7481 AN: 18288

GnomAD4 genome AF: 0.385 AC: 58313 AN: 151304 Hom.: 11612 Cov.: 29 AF XY: 0.385 AC XY: 28431 AN XY: 73898

African (AFR) AF: 0.292 AC: 12036 AN: 41208

American (AMR) AF: 0.396 AC: 6007 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1365 AN: 3468

East Asian (EAS) AF: 0.407 AC: 2073 AN: 5094

South Asian (SAS) AF: 0.384 AC: 1839 AN: 4786

European-Finnish (FIN) AF: 0.414 AC: 4339 AN: 10488

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29324 AN: 67764

Other (OTH) AF: 0.407 AC: 861 AN: 2114

Alfa AF: 0.403 Hom.: 7995

Bravo AF: 0.377

Asia WGS AF: 0.416 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		-0.022
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.95
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: rs2242449; hg19: chr17-7095507;