11-85482825-T-G

Variant names:

• chr11-85482825-T-G
• rs286499
• NM_001142699.3:c.40+115832A>C

Variant summary

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

The NM_001142699.3(DLG2):​c.40+115832A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,140 control chromosomes in the GnomAD database, including 59,801 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 0.88 (59801 hom., cov: 31)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.579
• Publications: 4 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 Gene-Disease associations (from GenCC):

• delayed puberty, self-limited

  Inheritance: AD, AR Classification: LIMITED Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.40+115832A>C		intron_variant	Intron 3 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.40+115832A>C		intron_variant	Intron 3 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.881 AC: 134000 AN: 152022 Hom.: 59795 Cov.: 31

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.893

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

GnomAD4 genome AF: 0.881 AC: 134046 AN: 152140 Hom.: 59801 Cov.: 31 AF XY: 0.875 AC XY: 65068 AN XY: 74378

African (AFR) AF: 0.766 AC: 31769 AN: 41468

American (AMR) AF: 0.839 AC: 12818 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3337 AN: 3472

East Asian (EAS) AF: 0.692 AC: 3573 AN: 5166

South Asian (SAS) AF: 0.790 AC: 3803 AN: 4812

European-Finnish (FIN) AF: 0.921 AC: 9758 AN: 10590

Middle Eastern (MID) AF: 0.969 AC: 285 AN: 294

European-Non Finnish (NFE) AF: 0.969 AC: 65924 AN: 68026

Other (OTH) AF: 0.890 AC: 1882 AN: 2114

Alfa AF: 0.916 Hom.: 3494

Bravo AF: 0.869

Asia WGS AF: 0.717 AC: 2494 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.1
DANN	Benign	0.79
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs286499; hg19: chr11-85193869;