chr11-84825592-T-C

Variant names:

• chr11-84825592-T-C
• rs1943699
• NM_001142699.3:c.357+286069A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001142699.3(DLG2):​c.357+286069A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,702 control chromosomes in the GnomAD database, including 16,706 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 0.45 (16706 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• 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 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.357+286069A>G		intron_variant	Intron 6 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.357+286069A>G		intron_variant	Intron 6 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68670 AN: 151584 Hom.: 16711 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.453 AC: 68657 AN: 151702 Hom.: 16706 Cov.: 32 AF XY: 0.447 AC XY: 33103 AN XY: 74116

African (AFR) AF: 0.276 AC: 11430 AN: 41438

American (AMR) AF: 0.445 AC: 6782 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2313 AN: 3460

East Asian (EAS) AF: 0.392 AC: 1992 AN: 5084

South Asian (SAS) AF: 0.482 AC: 2318 AN: 4808

European-Finnish (FIN) AF: 0.439 AC: 4641 AN: 10576

Middle Eastern (MID) AF: 0.548 AC: 160 AN: 292

European-Non Finnish (NFE) AF: 0.554 AC: 37566 AN: 67800

Other (OTH) AF: 0.487 AC: 1027 AN: 2108

Alfa AF: 0.523 Hom.: 81140

Bravo AF: 0.446

Asia WGS AF: 0.406 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		2.0
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: rs1943699; hg19: chr11-84536635;