11-84744316-T-G

Variant names:

• chr11-84744316-T-G
• rs6592199
• NM_001142699.3:c.358-209585A>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.358-209585A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,174 control chromosomes in the GnomAD database, including 2,617 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 0.17 (2617 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364
• 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

ENSG00000254787 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.358-209585A>C		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.358-209585A>C		intron_variant	Intron 6 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26139 AN: 152056 Hom.: 2618 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.0148

Gnomad SAS AF: 0.0662

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.172 AC: 26166 AN: 152174 Hom.: 2617 Cov.: 32 AF XY: 0.171 AC XY: 12746 AN XY: 74406

African (AFR) AF: 0.256 AC: 10623 AN: 41490

American (AMR) AF: 0.206 AC: 3155 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 491 AN: 3470

East Asian (EAS) AF: 0.0149 AC: 77 AN: 5184

South Asian (SAS) AF: 0.0663 AC: 320 AN: 4830

European-Finnish (FIN) AF: 0.168 AC: 1784 AN: 10590

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.134 AC: 9086 AN: 67994

Other (OTH) AF: 0.173 AC: 366 AN: 2114

Alfa AF: 0.119 Hom.: 646

Bravo AF: 0.183

Asia WGS AF: 0.0680 AC: 236 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	9.1
DANN	Benign	0.60
PhyloP100		0.36
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: rs6592199; hg19: chr11-84455359;