rs10501586

chr11-85045033-T-Cchr11-85045033-T-G

Variant summary

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

The NM_001142699.3(DLG2):c.357+66628A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 151,988 control chromosomes in the GnomAD database, including 3,555 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 0.20 (3555 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG2	NM_001142699.3	c.357+66628A>G		intron_variant		ENST00000376104.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG2	ENST00000376104.7	c.357+66628A>G		intron_variant		1	NM_001142699.3

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30924 AN: 151870 Hom.: 3550 Cov.: 32

Gnomad AFR AF: 0.0996

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.0625

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.204 AC: 30933 AN: 151988 Hom.: 3555 Cov.: 32 AF XY: 0.204 AC XY: 15135 AN XY: 74296

Gnomad4 AFR AF: 0.0994

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.0623

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.217

Alfa AF: 0.228 Hom.: 1142

Bravo AF: 0.196

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.2
Dann	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10501586; hg19: chr11-84756077;