11-85306432-A-G

Variant names:

• chr11-85306432-A-G
• rs17148090
• NM_001142699.3:c.41-21067T>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.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
• Publications: 13 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0939 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG2	NM_001142699.3	MANE Select	c.41-21067T>C		intron	N/A	NP_001136171.1
	DLG2	NM_001351274.2		c.152-21067T>C		intron	N/A	NP_001338203.1
	DLG2	NM_001351275.2		c.152-21067T>C		intron	N/A	NP_001338204.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLG2	ENST00000376104.7	TSL:1 MANE Select	c.41-21067T>C		intron	N/A	ENSP00000365272.2
	DLG2	ENST00000650630.1		c.152-21067T>C		intron	N/A	ENSP00000497771.1
	DLG2	ENST00000706226.1		c.152-21067T>C		intron	N/A	ENSP00000516284.1

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

African (AFR) AF: 0.0847 AC: 3521 AN: 41552

American (AMR) AF: 0.0570 AC: 871 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0789 AC: 274 AN: 3472

East Asian (EAS) AF: 0.0965 AC: 499 AN: 5170

South Asian (SAS) AF: 0.101 AC: 489 AN: 4826

European-Finnish (FIN) AF: 0.0705 AC: 748 AN: 10608

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0660 AC: 4490 AN: 68000

Other (OTH) AF: 0.0643 AC: 136 AN: 2114

Alfa AF: 0.0685 Hom.: 1387

Bravo AF: 0.0735

Asia WGS AF: 0.0880 AC: 306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.48
DANN	Benign	0.67
PhyloP100		-0.51
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: rs17148090; hg19: chr11-85017476;