11-85592260-T-C

Variant names:

• chr11-85592260-T-C
• rs631375
• NM_001142699.3:c.40+6397A>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.40+6397A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,112 control chromosomes in the GnomAD database, including 12,911 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 0.41 (12911 hom., cov: 33)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775
• Publications: 5 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.40+6397A>G		intron_variant	Intron 3 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.40+6397A>G		intron_variant	Intron 3 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62024 AN: 151992 Hom.: 12878 Cov.: 33

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.386

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.408 AC: 62106 AN: 152112 Hom.: 12911 Cov.: 33 AF XY: 0.411 AC XY: 30540 AN XY: 74346

African (AFR) AF: 0.416 AC: 17254 AN: 41492

American (AMR) AF: 0.452 AC: 6915 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1327 AN: 3466

East Asian (EAS) AF: 0.525 AC: 2719 AN: 5176

South Asian (SAS) AF: 0.507 AC: 2448 AN: 4824

European-Finnish (FIN) AF: 0.357 AC: 3779 AN: 10574

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.386 AC: 26273 AN: 67980

Other (OTH) AF: 0.421 AC: 890 AN: 2114

Alfa AF: 0.395 Hom.: 4460

Bravo AF: 0.419

Asia WGS AF: 0.512 AC: 1785 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.82
PhyloP100		-0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs631375; hg19: chr11-85303304;