rs877984

Variant names:

• chr11-83868777-T-A
• rs877984
• NM_001142699.3:c.1565+5643A>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.1565+5643A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,792 control chromosomes in the GnomAD database, including 23,585 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 0.56 (23585 hom., cov: 30)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.1565+5643A>T		intron_variant	Intron 16 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.1565+5643A>T		intron_variant	Intron 16 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84208 AN: 151674 Hom.: 23574 Cov.: 30

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.581

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

GnomAD4 genome AF: 0.555 AC: 84262 AN: 151792 Hom.: 23585 Cov.: 30 AF XY: 0.554 AC XY: 41093 AN XY: 74168

African (AFR) AF: 0.540 AC: 22337 AN: 41392

American (AMR) AF: 0.567 AC: 8631 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2052 AN: 3468

East Asian (EAS) AF: 0.568 AC: 2924 AN: 5146

South Asian (SAS) AF: 0.435 AC: 2091 AN: 4808

European-Finnish (FIN) AF: 0.563 AC: 5925 AN: 10526

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.563 AC: 38265 AN: 67916

Other (OTH) AF: 0.583 AC: 1231 AN: 2112

Alfa AF: 0.569 Hom.: 3053

Bravo AF: 0.557

Asia WGS AF: 0.539 AC: 1877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.72
PhyloP100		-1.8
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: rs877984; hg19: chr11-83579820;