11-84642251-G-C

Variant names:

• chr11-84642251-G-C
• rs1940078
• NM_001142699.3:c.358-107520C>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.358-107520C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 151,414 control chromosomes in the GnomAD database, including 66,113 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 0.93 (66113 hom., cov: 25)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.358-107520C>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.358-107520C>G		intron_variant	Intron 6 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.934 AC: 141241 AN: 151296 Hom.: 66052 Cov.: 25

Gnomad AFR AF: 0.982

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.922

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.964

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.897

Gnomad OTH AF: 0.935

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

GnomAD4 genome AF: 0.934 AC: 141361 AN: 151414 Hom.: 66113 Cov.: 25 AF XY: 0.937 AC XY: 69334 AN XY: 73990

African (AFR) AF: 0.982 AC: 40544 AN: 41288

American (AMR) AF: 0.934 AC: 14189 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.922 AC: 3197 AN: 3466

East Asian (EAS) AF: 0.996 AC: 5035 AN: 5056

South Asian (SAS) AF: 0.963 AC: 4599 AN: 4776

European-Finnish (FIN) AF: 0.949 AC: 9952 AN: 10488

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.897 AC: 60875 AN: 67848

Other (OTH) AF: 0.936 AC: 1959 AN: 2094

Alfa AF: 0.895 Hom.: 3356

Bravo AF: 0.934

Asia WGS AF: 0.979 AC: 3400 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.018
DANN	Benign	0.36
PhyloP100		-3.2
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: rs1940078; hg19: chr11-84353294;