11-84321687-G-C

Variant names:

• chr11-84321687-G-C
• rs1399619
• NM_001142699.3:c.520-70396C>G

Variant summary

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

The ENST00000376104.7(DLG2):​c.520-70396C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,956 control chromosomes in the GnomAD database, including 13,505 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 0.42 (13505 hom., cov: 32)
• Consequence: DLG2 ENST00000376104.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602
• Publications: 1 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000376104.7. 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.520-70396C>G		intron	N/A	NP_001136171.1
	DLG2	NM_001351274.2		c.556-70396C>G		intron	N/A	NP_001338203.1
	DLG2	NM_001351275.2		c.553-70396C>G		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.520-70396C>G		intron	N/A	ENSP00000365272.2
	DLG2	ENST00000398309.6	TSL:1	c.205-70396C>G		intron	N/A	ENSP00000381355.2
	DLG2	ENST00000532653.5	TSL:1	c.205-70396C>G		intron	N/A	ENSP00000435849.1

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63584 AN: 151836 Hom.: 13499 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.419 AC: 63609 AN: 151956 Hom.: 13505 Cov.: 32 AF XY: 0.418 AC XY: 31064 AN XY: 74250

African (AFR) AF: 0.388 AC: 16082 AN: 41434

American (AMR) AF: 0.388 AC: 5922 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1310 AN: 3468

East Asian (EAS) AF: 0.612 AC: 3141 AN: 5132

South Asian (SAS) AF: 0.441 AC: 2125 AN: 4816

European-Finnish (FIN) AF: 0.415 AC: 4378 AN: 10550

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29079 AN: 67966

Other (OTH) AF: 0.408 AC: 861 AN: 2112

Alfa AF: 0.300 Hom.: 751

Bravo AF: 0.414

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.89
DANN	Benign	0.31
PhyloP100		-0.60
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: rs1399619; hg19: chr11-84032730;