rs1452928

Variant names:

• chr11-85111277-G-C
• rs1452928
• NM_001142699.3:c.357+384C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-85111277-G-C
• chr11-85111277-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142699.3(DLG2):​c.357+384C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,038 control chromosomes in the GnomAD database, including 4,080 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 0.23 (4080 hom., cov: 33)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 10 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):

• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• delayed puberty, self-limited

  Inheritance: AR, 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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142699.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG2	NM_001142699.3	MANE Select	c.357+384C>G		intron	N/A	NP_001136171.1	Q15700-2
	DLG2	NM_001351274.2		c.393+43279C>G		intron	N/A	NP_001338203.1	A0A994J819
	DLG2	NM_001351275.2		c.393+43279C>G		intron	N/A	NP_001338204.1	A0A994J7P1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG2	ENST00000376104.7	TSL:1 MANE Select	c.357+384C>G		intron	N/A	ENSP00000365272.2	Q15700-2
	DLG2	ENST00000650630.1		c.468+384C>G		intron	N/A	ENSP00000497771.1	A0A3B3ITF1
	DLG2	ENST00000706226.1		c.393+43279C>G		intron	N/A	ENSP00000516284.1	A0A994J819

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34177 AN: 151922 Hom.: 4069 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.0625

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.225 AC: 34214 AN: 152038 Hom.: 4080 Cov.: 33 AF XY: 0.225 AC XY: 16745 AN XY: 74314

African (AFR) AF: 0.185 AC: 7678 AN: 41494

American (AMR) AF: 0.263 AC: 4006 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1283 AN: 3464

East Asian (EAS) AF: 0.0622 AC: 321 AN: 5160

South Asian (SAS) AF: 0.265 AC: 1277 AN: 4820

European-Finnish (FIN) AF: 0.233 AC: 2463 AN: 10580

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16380 AN: 67964

Other (OTH) AF: 0.224 AC: 474 AN: 2114

Alfa AF: 0.216 Hom.: 2170

Bravo AF: 0.223

Asia WGS AF: 0.161 AC: 558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.5
DANN	Benign	0.53
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1452928; hg19: chr11-84822321;