rs17507049

Variant names:

• chr11-84303524-A-G
• rs17507049
• NM_001142699.3:c.520-52233T>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.520-52233T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,264 control chromosomes in the GnomAD database, including 927 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 0.10 (927 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.851
• 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=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.520-52233T>C		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.520-52233T>C		intron_variant	Intron 7 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15599 AN: 152146 Hom.: 927 Cov.: 32

Gnomad AFR AF: 0.0574

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0908

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.102 AC: 15600 AN: 152264 Hom.: 927 Cov.: 32 AF XY: 0.102 AC XY: 7559 AN XY: 74464

African (AFR) AF: 0.0574 AC: 2386 AN: 41560

American (AMR) AF: 0.0804 AC: 1230 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3472

East Asian (EAS) AF: 0.0908 AC: 470 AN: 5176

South Asian (SAS) AF: 0.129 AC: 622 AN: 4832

European-Finnish (FIN) AF: 0.115 AC: 1217 AN: 10606

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8776 AN: 68004

Other (OTH) AF: 0.110 AC: 233 AN: 2112

Alfa AF: 0.0964 Hom.: 396

Bravo AF: 0.0973

Asia WGS AF: 0.0900 AC: 311 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.9
DANN	Benign	0.76
PhyloP100		0.85
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: rs17507049; hg19: chr11-84014567;