11-85061380-C-T

Variant names:

• chr11-85061380-C-T
• rs686009
• NM_001142699.3:c.357+50281G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142699.3(DLG2):​c.357+50281G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 151,526 control chromosomes in the GnomAD database, including 34,471 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 0.66 (34471 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142699.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG2	NM_001142699.3	MANE Select	c.357+50281G>A		intron	N/A	NP_001136171.1
	DLG2	NM_001351274.2		c.393+93176G>A		intron	N/A	NP_001338203.1
	DLG2	NM_001351275.2		c.393+93176G>A		intron	N/A	NP_001338204.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG2	ENST00000376104.7	TSL:1 MANE Select	c.357+50281G>A		intron	N/A	ENSP00000365272.2
	DLG2	ENST00000650630.1		c.468+50281G>A		intron	N/A	ENSP00000497771.1
	DLG2	ENST00000706226.1		c.393+93176G>A		intron	N/A	ENSP00000516284.1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 100666 AN: 151406 Hom.: 34433 Cov.: 32

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.665 AC: 100750 AN: 151526 Hom.: 34471 Cov.: 32 AF XY: 0.665 AC XY: 49225 AN XY: 74042

African (AFR) AF: 0.812 AC: 33633 AN: 41402

American (AMR) AF: 0.633 AC: 9590 AN: 15146

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1840 AN: 3452

East Asian (EAS) AF: 0.930 AC: 4785 AN: 5144

South Asian (SAS) AF: 0.663 AC: 3200 AN: 4830

European-Finnish (FIN) AF: 0.555 AC: 5847 AN: 10536

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39615 AN: 67716

Other (OTH) AF: 0.683 AC: 1430 AN: 2094

Alfa AF: 0.638 Hom.: 4558

Bravo AF: 0.681

Asia WGS AF: 0.802 AC: 2789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	7.0
DANN	Benign	0.58
PhyloP100		1.1
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: rs686009; hg19: chr11-84772424;