11-85306432-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142699.3(DLG2):c.41-21067T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0739 in 152,242 control chromosomes in the GnomAD database, including 447 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 0.074 (447 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0939 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG2	NM_001142699.3	c.41-21067T>C		intron_variant		ENST00000376104.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG2	ENST00000376104.7	c.41-21067T>C		intron_variant		1	NM_001142699.3

Frequencies

GnomAD3 genomes AF: 0.0739 AC: 11245 AN: 152124 Hom.: 447 Cov.: 32

Gnomad AFR AF: 0.0846

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0789

Gnomad EAS AF: 0.0971

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0705

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0661

Gnomad OTH AF: 0.0655

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

GnomAD4 genome AF: 0.0739 AC: 11249 AN: 152242 Hom.: 447 Cov.: 32 AF XY: 0.0748 AC XY: 5571 AN XY: 74452

Gnomad4 AFR AF: 0.0847

Gnomad4 AMR AF: 0.0570

Gnomad4 ASJ AF: 0.0789

Gnomad4 EAS AF: 0.0965

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0705

Gnomad4 NFE AF: 0.0660

Gnomad4 OTH AF: 0.0643

Alfa AF: 0.0679 Hom.: 576

Bravo AF: 0.0735

Asia WGS AF: 0.0880 AC: 306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.48
Dann	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17148090; hg19: chr11-85017476;