rs3815988

Variant names:

• chr11-83532989-G-A
• rs3815988
• NM_001142699.3:c.2118-206C>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.2118-206C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,070 control chromosomes in the GnomAD database, including 35,848 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 0.68 (35848 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.2118-206C>T		intron_variant	Intron 20 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.2118-206C>T		intron_variant	Intron 20 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103126 AN: 151952 Hom.: 35809 Cov.: 32

Gnomad AFR AF: 0.805

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.679 AC: 103203 AN: 152070 Hom.: 35848 Cov.: 32 AF XY: 0.676 AC XY: 50259 AN XY: 74316

African (AFR) AF: 0.806 AC: 33445 AN: 41512

American (AMR) AF: 0.507 AC: 7747 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2127 AN: 3470

East Asian (EAS) AF: 0.548 AC: 2833 AN: 5170

South Asian (SAS) AF: 0.651 AC: 3141 AN: 4822

European-Finnish (FIN) AF: 0.703 AC: 7430 AN: 10568

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44095 AN: 67946

Other (OTH) AF: 0.678 AC: 1429 AN: 2108

Alfa AF: 0.652 Hom.: 5779

Bravo AF: 0.670

Asia WGS AF: 0.597 AC: 2076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.65
PhyloP100		-0.87
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: rs3815988; hg19: chr11-83244032;