rs7928811

Variant names:

• chr11-84105439-T-G
• rs7928811
• NM_001142699.3:c.625-6392A>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.625-6392A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 152,036 control chromosomes in the GnomAD database, including 23,955 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 (23955 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 6 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.625-6392A>C		intron_variant	Intron 9 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.625-6392A>C		intron_variant	Intron 9 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77648 AN: 151916 Hom.: 23956 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.511 AC: 77642 AN: 152036 Hom.: 23955 Cov.: 32 AF XY: 0.505 AC XY: 37516 AN XY: 74300

African (AFR) AF: 0.143 AC: 5942 AN: 41488

American (AMR) AF: 0.623 AC: 9510 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2379 AN: 3468

East Asian (EAS) AF: 0.530 AC: 2734 AN: 5154

South Asian (SAS) AF: 0.592 AC: 2852 AN: 4820

European-Finnish (FIN) AF: 0.537 AC: 5671 AN: 10562

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46510 AN: 67954

Other (OTH) AF: 0.575 AC: 1214 AN: 2112

Alfa AF: 0.547 Hom.: 21303

Bravo AF: 0.502

Asia WGS AF: 0.539 AC: 1874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.0
DANN	Benign	0.73
PhyloP100		-0.19
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: rs7928811; hg19: chr11-83816482;