chr11-84706803-T-C

Variant names:

• chr11-84706803-T-C
• rs10501570
• NM_001142699.3:c.358-172072A>G

Variant summary

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

The NM_001142699.3(DLG2):​c.358-172072A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 151,776 control chromosomes in the GnomAD database, including 1,997 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 0.14 (1997 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46
• Publications: 21 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.358-172072A>G		intron_variant	Intron 6 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.358-172072A>G		intron_variant	Intron 6 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21377 AN: 151658 Hom.: 1998 Cov.: 32

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.0199

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.141 AC: 21378 AN: 151776 Hom.: 1997 Cov.: 32 AF XY: 0.144 AC XY: 10673 AN XY: 74170

African (AFR) AF: 0.0343 AC: 1425 AN: 41492

American (AMR) AF: 0.190 AC: 2897 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 438 AN: 3460

East Asian (EAS) AF: 0.0199 AC: 102 AN: 5124

South Asian (SAS) AF: 0.109 AC: 528 AN: 4824

European-Finnish (FIN) AF: 0.237 AC: 2510 AN: 10580

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12854 AN: 67766

Other (OTH) AF: 0.140 AC: 296 AN: 2110

Alfa AF: 0.169 Hom.: 6425

Bravo AF: 0.135

Asia WGS AF: 0.0690 AC: 240 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.014
DANN	Benign	0.25
PhyloP100		-3.5
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: rs10501570; hg19: chr11-84417846;