11-83694836-G-A

Variant names:

• chr11-83694836-G-A
• rs12225388
• NM_001142699.3:c.1826-61511C>T

Variant summary

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

The NM_001142699.3(DLG2):​c.1826-61511C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,148 control chromosomes in the GnomAD database, including 7,819 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 0.28 (7819 hom., cov: 33)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.643
• Publications: 3 publications found

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]

DLG2-AS2 (HGNC:40179): (DLG2 antisense RNA 2)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.1826-61511C>T		intron_variant	Intron 18 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.1826-61511C>T		intron_variant	Intron 18 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43031 AN: 152030 Hom.: 7783 Cov.: 33

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.283 AC: 43115 AN: 152148 Hom.: 7819 Cov.: 33 AF XY: 0.285 AC XY: 21233 AN XY: 74388

African (AFR) AF: 0.515 AC: 21392 AN: 41506

American (AMR) AF: 0.152 AC: 2327 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 782 AN: 3470

East Asian (EAS) AF: 0.148 AC: 764 AN: 5172

South Asian (SAS) AF: 0.239 AC: 1149 AN: 4814

European-Finnish (FIN) AF: 0.300 AC: 3174 AN: 10580

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12737 AN: 68006

Other (OTH) AF: 0.240 AC: 506 AN: 2106

Alfa AF: 0.191 Hom.: 1541

Bravo AF: 0.280

Asia WGS AF: 0.218 AC: 764 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.5
DANN	Benign	0.69
PhyloP100		0.64
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: rs12225388; hg19: chr11-83405879;