11-84299186-A-T

Variant names:

• chr11-84299186-A-T
• rs1399622
• NM_001142699.3:c.520-47895T>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.520-47895T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,174 control chromosomes in the GnomAD database, including 47,991 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 0.79 (47991 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.476
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 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.520-47895T>A		intron	N/A	NP_001136171.1
	DLG2	NM_001351274.2		c.556-47895T>A		intron	N/A	NP_001338203.1
	DLG2	NM_001351275.2		c.553-47895T>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.520-47895T>A		intron	N/A	ENSP00000365272.2
	DLG2	ENST00000398309.6	TSL:1	c.205-47895T>A		intron	N/A	ENSP00000381355.2
	DLG2	ENST00000532653.5	TSL:1	c.205-47895T>A		intron	N/A	ENSP00000435849.1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119537 AN: 152056 Hom.: 47928 Cov.: 32

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.724

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.786 AC: 119660 AN: 152174 Hom.: 47991 Cov.: 32 AF XY: 0.787 AC XY: 58524 AN XY: 74402

African (AFR) AF: 0.947 AC: 39365 AN: 41550

American (AMR) AF: 0.809 AC: 12380 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2227 AN: 3468

East Asian (EAS) AF: 0.903 AC: 4665 AN: 5166

South Asian (SAS) AF: 0.697 AC: 3360 AN: 4820

European-Finnish (FIN) AF: 0.724 AC: 7666 AN: 10586

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

European-Non Finnish (NFE) AF: 0.699 AC: 47522 AN: 67972

Other (OTH) AF: 0.766 AC: 1618 AN: 2112

Alfa AF: 0.667 Hom.: 2167

Bravo AF: 0.802

Asia WGS AF: 0.834 AC: 2895 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.73
DANN	Benign	0.30
PhyloP100		-0.48
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: rs1399622; hg19: chr11-84010229;