11-83909744-A-G

Variant names:

• chr11-83909744-A-G
• rs790356
• NM_001142699.3:c.1496+20584T>C

Variant summary

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

The NM_001142699.3(DLG2):​c.1496+20584T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,066 control chromosomes in the GnomAD database, including 19,875 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 0.51 (19875 hom., cov: 33)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370
• Publications: 27 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

LOC124902729 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.1496+20584T>C		intron_variant	Intron 15 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.1496+20584T>C		intron_variant	Intron 15 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76845 AN: 151948 Hom.: 19870 Cov.: 33

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.506 AC: 76881 AN: 152066 Hom.: 19875 Cov.: 33 AF XY: 0.508 AC XY: 37767 AN XY: 74344

African (AFR) AF: 0.428 AC: 17758 AN: 41500

American (AMR) AF: 0.550 AC: 8392 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1760 AN: 3468

East Asian (EAS) AF: 0.854 AC: 4410 AN: 5166

South Asian (SAS) AF: 0.537 AC: 2591 AN: 4824

European-Finnish (FIN) AF: 0.514 AC: 5438 AN: 10584

Middle Eastern (MID) AF: 0.592 AC: 173 AN: 292

European-Non Finnish (NFE) AF: 0.511 AC: 34718 AN: 67956

Other (OTH) AF: 0.508 AC: 1073 AN: 2112

Alfa AF: 0.513 Hom.: 89687

Bravo AF: 0.507

Asia WGS AF: 0.660 AC: 2296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	4.9
DANN	Benign	0.85
PhyloP100		0.037
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: rs790356; hg19: chr11-83620787;