rs921452

Positions:

• chr11-83745148-C-T

Variant summary

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

The NM_001142699.3(DLG2):​c.1825+41542G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,130 control chromosomes in the GnomAD database, including 1,574 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 0.13 (1574 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG2	NM_001142699.3	c.1825+41542G>A		intron_variant		ENST00000376104.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG2	ENST00000376104.7	c.1825+41542G>A		intron_variant		1	NM_001142699.3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20290 AN: 152012 Hom.: 1569 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.0792

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.134 AC: 20322 AN: 152130 Hom.: 1574 Cov.: 32 AF XY: 0.135 AC XY: 10062 AN XY: 74370

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.0791

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.125

Alfa AF: 0.131 Hom.: 185

Bravo AF: 0.132

Asia WGS AF: 0.181 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.76

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: rs921452; hg19: chr11-83456191;