NM_001142699.3:c.358-252042T>C

Variant names:

• chr11-84786773-A-G
• rs10501572
• NM_001142699.3:c.358-252042T>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.358-252042T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,014 control chromosomes in the GnomAD database, including 6,257 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 0.27 (6257 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.281
• Publications: 1 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=-0.56).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.358-252042T>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.358-252042T>C		intron_variant	Intron 6 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41540 AN: 151896 Hom.: 6260 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.273 AC: 41551 AN: 152014 Hom.: 6257 Cov.: 32 AF XY: 0.280 AC XY: 20789 AN XY: 74322

African (AFR) AF: 0.186 AC: 7712 AN: 41452

American (AMR) AF: 0.315 AC: 4805 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 920 AN: 3468

East Asian (EAS) AF: 0.0240 AC: 124 AN: 5170

South Asian (SAS) AF: 0.259 AC: 1248 AN: 4818

European-Finnish (FIN) AF: 0.433 AC: 4575 AN: 10556

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21048 AN: 67972

Other (OTH) AF: 0.268 AC: 566 AN: 2114

Alfa AF: 0.279 Hom.: 776

Bravo AF: 0.262

Asia WGS AF: 0.152 AC: 531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	3.1
DANN	Benign	0.73
PhyloP100		0.28
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: rs10501572; hg19: chr11-84497816;