rs507506

Variant names:

• chr17-7215003-A-G
• rs507506
• NM_001321075.3:c.30+2115T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-7215003-A-G
• chr17-7215003-A-T

Variant summary

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

The NM_001321075.3(DLG4):​c.30+2115T>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 151,982 control chromosomes in the GnomAD database, including 23,253 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 (23253 hom., cov: 31)
• Consequence: DLG4 NM_001321075.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.671
• Publications: 45 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=-0.64).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG4	NM_001321075.3	c.30+2115T>C		intron_variant	Intron 1 of 19	ENST00000399506.9	NP_001308004.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG4	ENST00000399506.9	c.30+2115T>C		intron_variant	Intron 1 of 19	2	NM_001321075.3	ENSP00000382425.2
DLG4	ENST00000648172.9	c.159+3238T>C		intron_variant	Intron 3 of 21			ENSP00000497806.3
DLG4	ENST00000647975.1	c.30+2115T>C		intron_variant	Intron 1 of 6			ENSP00000497912.1
DLG4	ENST00000491753.2	n.159+3238T>C		intron_variant	Intron 3 of 20	2		ENSP00000467897.2

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83132 AN: 151862 Hom.: 23229 Cov.: 31

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.547 AC: 83195 AN: 151982 Hom.: 23253 Cov.: 31 AF XY: 0.551 AC XY: 40972 AN XY: 74302

African (AFR) AF: 0.430 AC: 17816 AN: 41420

American (AMR) AF: 0.540 AC: 8242 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2012 AN: 3470

East Asian (EAS) AF: 0.485 AC: 2501 AN: 5154

South Asian (SAS) AF: 0.624 AC: 3011 AN: 4828

European-Finnish (FIN) AF: 0.652 AC: 6897 AN: 10572

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40787 AN: 67954

Other (OTH) AF: 0.581 AC: 1225 AN: 2108

Alfa AF: 0.562 Hom.: 25784

Bravo AF: 0.531

Asia WGS AF: 0.566 AC: 1971 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		0.67
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: rs507506; hg19: chr17-7118322;