11-83751970-T-C

Variant names:

• chr11-83751970-T-C
• rs7109065
• NM_001142699.3:c.1825+34720A>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.1825+34720A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 151,936 control chromosomes in the GnomAD database, including 5,015 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 0.22 (5015 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.460
• Publications: 3 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 (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.1825+34720A>G		intron_variant	Intron 18 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.1825+34720A>G		intron_variant	Intron 18 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33174 AN: 151818 Hom.: 4981 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.219 AC: 33257 AN: 151936 Hom.: 5015 Cov.: 32 AF XY: 0.219 AC XY: 16287 AN XY: 74282

African (AFR) AF: 0.428 AC: 17749 AN: 41422

American (AMR) AF: 0.116 AC: 1770 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3466

East Asian (EAS) AF: 0.133 AC: 690 AN: 5172

South Asian (SAS) AF: 0.219 AC: 1054 AN: 4804

European-Finnish (FIN) AF: 0.154 AC: 1623 AN: 10572

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9146 AN: 67916

Other (OTH) AF: 0.197 AC: 416 AN: 2110

Alfa AF: 0.180 Hom.: 934

Bravo AF: 0.224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.5
DANN	Benign	0.73
PhyloP100		0.46
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: rs7109065; hg19: chr11-83463013;