rs10501561

Positions:

• chr11-84396974-C-G

Variant summary

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

The NM_001142699.3(DLG2):​c.519+137596G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,146 control chromosomes in the GnomAD database, including 2,336 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 0.15 (2336 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG2	NM_001142699.3	c.519+137596G>C		intron_variant		ENST00000376104.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG2	ENST00000376104.7	c.519+137596G>C		intron_variant		1	NM_001142699.3

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22602 AN: 152028 Hom.: 2334 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0789

Gnomad ASJ AF: 0.0869

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.149 AC: 22627 AN: 152146 Hom.: 2336 Cov.: 32 AF XY: 0.141 AC XY: 10503 AN XY: 74394

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.0787

Gnomad4 ASJ AF: 0.0869

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.0614

Gnomad4 FIN AF: 0.0388

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.130

Alfa AF: 0.132 Hom.: 209

Bravo AF: 0.157

Asia WGS AF: 0.0570 AC: 198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.016
DANN	Benign	0.52

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: rs10501561; hg19: chr11-84108017;