11-83744664-T-C

Variant names:

• chr11-83744664-T-C
• rs3885683
• NM_001142699.3:c.1825+42026A>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+42026A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0903 in 152,218 control chromosomes in the GnomAD database, including 859 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 0.090 (859 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.1825+42026A>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+42026A>G		intron_variant	Intron 18 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.0904 AC: 13751 AN: 152100 Hom.: 859 Cov.: 32

Gnomad AFR AF: 0.0215

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.0683

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0394

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0948

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

GnomAD4 genome AF: 0.0903 AC: 13741 AN: 152218 Hom.: 859 Cov.: 32 AF XY: 0.0894 AC XY: 6649 AN XY: 74404

African (AFR) AF: 0.0214 AC: 890 AN: 41568

American (AMR) AF: 0.0682 AC: 1043 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 393 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0392 AC: 189 AN: 4824

European-Finnish (FIN) AF: 0.183 AC: 1939 AN: 10582

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9029 AN: 67992

Other (OTH) AF: 0.0934 AC: 197 AN: 2110

Alfa AF: 0.108 Hom.: 1975

Bravo AF: 0.0788

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	13
DANN	Benign	0.60
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs3885683; hg19: chr11-83455707;