rs62388

Variant names:

• chr11-85509117-G-A
• rs62388
• NM_001142699.3:c.40+89540C>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.40+89540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,038 control chromosomes in the GnomAD database, including 59,210 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 0.88 (59210 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• 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 (NFE) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.40+89540C>T		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+89540C>T		intron_variant	Intron 3 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.881 AC: 133856 AN: 151920 Hom.: 59196 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.881 AC: 133915 AN: 152038 Hom.: 59210 Cov.: 32 AF XY: 0.874 AC XY: 64961 AN XY: 74312

African (AFR) AF: 0.885 AC: 36742 AN: 41512

American (AMR) AF: 0.823 AC: 12538 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3162 AN: 3468

East Asian (EAS) AF: 0.694 AC: 3568 AN: 5144

South Asian (SAS) AF: 0.774 AC: 3737 AN: 4826

European-Finnish (FIN) AF: 0.859 AC: 9104 AN: 10594

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62120 AN: 67946

Other (OTH) AF: 0.872 AC: 1841 AN: 2112

Alfa AF: 0.889 Hom.: 9415

Bravo AF: 0.875

Asia WGS AF: 0.713 AC: 2476 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.34
DANN	Benign	0.47
PhyloP100		-0.23
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: rs62388; hg19: chr11-85220161;