rs1155310

Variant names:

• chr11-83778321-G-A
• rs1155310
• NM_001142699.3:c.1825+8369C>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.1825+8369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,934 control chromosomes in the GnomAD database, including 4,759 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 0.22 (4759 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0900
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.1825+8369C>T		intron_variant	Intron 18 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.1825+8369C>T		intron_variant	Intron 18 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33649 AN: 151816 Hom.: 4734 Cov.: 32

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.222 AC: 33712 AN: 151934 Hom.: 4759 Cov.: 32 AF XY: 0.222 AC XY: 16490 AN XY: 74268

African (AFR) AF: 0.398 AC: 16464 AN: 41400

American (AMR) AF: 0.123 AC: 1874 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3460

East Asian (EAS) AF: 0.117 AC: 604 AN: 5166

South Asian (SAS) AF: 0.240 AC: 1154 AN: 4812

European-Finnish (FIN) AF: 0.171 AC: 1809 AN: 10572

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10548 AN: 67924

Other (OTH) AF: 0.198 AC: 420 AN: 2116

Alfa AF: 0.174 Hom.: 6579

Bravo AF: 0.224

Asia WGS AF: 0.199 AC: 695 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.8
DANN	Benign	0.69
PhyloP100		0.090
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: rs1155310; hg19: chr11-83489364;