NM_001142699.3:c.1825+13254C>G

Variant names:

• chr11-83773436-G-C
• rs2044863
• NM_001142699.3:c.1825+13254C>G

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+13254C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,080 control chromosomes in the GnomAD database, including 2,961 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 0.18 (2961 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374
• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.1825+13254C>G		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+13254C>G		intron_variant	Intron 18 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27349 AN: 151962 Hom.: 2955 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.180 AC: 27385 AN: 152080 Hom.: 2961 Cov.: 32 AF XY: 0.179 AC XY: 13333 AN XY: 74336

African (AFR) AF: 0.298 AC: 12371 AN: 41454

American (AMR) AF: 0.102 AC: 1561 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3472

East Asian (EAS) AF: 0.116 AC: 599 AN: 5184

South Asian (SAS) AF: 0.222 AC: 1068 AN: 4820

European-Finnish (FIN) AF: 0.113 AC: 1195 AN: 10576

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9501 AN: 67976

Other (OTH) AF: 0.164 AC: 347 AN: 2110

Alfa AF: 0.164 Hom.: 310

Bravo AF: 0.182

Asia WGS AF: 0.178 AC: 622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.9
DANN	Benign	0.71
PhyloP100		0.37
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: rs2044863; hg19: chr11-83484479;