11-83919539-C-T

Variant names:

• chr11-83919539-C-T
• rs1483394
• NM_001142699.3:c.1496+10789G>A

Variant summary

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

The NM_001142699.3(DLG2):​c.1496+10789G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,140 control chromosomes in the GnomAD database, including 48,769 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 0.80 (48769 hom., cov: 33)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 2 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

LOC124902729 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.1496+10789G>A		intron_variant	Intron 15 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.1496+10789G>A		intron_variant	Intron 15 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121638 AN: 152022 Hom.: 48732 Cov.: 33

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.816

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.800 AC: 121730 AN: 152140 Hom.: 48769 Cov.: 33 AF XY: 0.801 AC XY: 59564 AN XY: 74354

African (AFR) AF: 0.819 AC: 34011 AN: 41522

American (AMR) AF: 0.748 AC: 11428 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.816 AC: 2834 AN: 3472

East Asian (EAS) AF: 0.909 AC: 4707 AN: 5180

South Asian (SAS) AF: 0.873 AC: 4215 AN: 4826

European-Finnish (FIN) AF: 0.781 AC: 8247 AN: 10562

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.789 AC: 53661 AN: 67990

Other (OTH) AF: 0.797 AC: 1681 AN: 2110

Alfa AF: 0.791 Hom.: 9895

Bravo AF: 0.800

Asia WGS AF: 0.872 AC: 3034 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.87
DANN	Benign	0.32
PhyloP100		-0.14
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: rs1483394; hg19: chr11-83630582;