rs518143

Positions:

• chr11-83624721-A-G
• chr11-83624721-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142699.3(DLG2):​c.1940+8490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,134 control chromosomes in the GnomAD database, including 8,044 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 0.30 (8044 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.866

Genes affected

DLG2 (HGNC:2901): (discs large MAGUK scaffold protein 2) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. The encoded protein forms a heterodimer with a related family member that 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. Additional transcript variants have been described, but their full-length nature is not known. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG2	NM_001142699.3	c.1940+8490T>C		intron_variant		ENST00000376104.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG2	ENST00000376104.7	c.1940+8490T>C		intron_variant		1	NM_001142699.3

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45907 AN: 152016 Hom.: 8031 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.302 AC: 45934 AN: 152134 Hom.: 8044 Cov.: 32 AF XY: 0.306 AC XY: 22792 AN XY: 74376

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.308

Alfa AF: 0.324 Hom.: 1102

Bravo AF: 0.304

Asia WGS AF: 0.406 AC: 1411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.71

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

LitVar

Other links and lift over

dbSNP: rs518143; hg19: chr11-83335764;