rs10501563

Variant names:

• chr11-84469560-T-A
• rs10501563
• NM_001142699.3:c.519+65010A>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.519+65010A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 151,470 control chromosomes in the GnomAD database, including 4,573 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 0.24 (4573 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.519+65010A>T		intron_variant	Intron 7 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.519+65010A>T		intron_variant	Intron 7 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36458 AN: 151352 Hom.: 4558 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.241 AC: 36504 AN: 151470 Hom.: 4573 Cov.: 32 AF XY: 0.233 AC XY: 17223 AN XY: 74004

African (AFR) AF: 0.257 AC: 10638 AN: 41398

American (AMR) AF: 0.173 AC: 2623 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 608 AN: 3456

East Asian (EAS) AF: 0.229 AC: 1174 AN: 5116

South Asian (SAS) AF: 0.370 AC: 1783 AN: 4818

European-Finnish (FIN) AF: 0.123 AC: 1296 AN: 10576

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.260 AC: 17588 AN: 67626

Other (OTH) AF: 0.247 AC: 519 AN: 2104

Alfa AF: 0.239 Hom.: 559

Bravo AF: 0.241

Asia WGS AF: 0.304 AC: 1059 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.64
PhyloP100		0.49
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: rs10501563; hg19: chr11-84180603;