chr11-84456792-G-A

Variant names:

• chr11-84456792-G-A
• rs7952143
• NM_001142699.3:c.519+77778C>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.519+77778C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 150,970 control chromosomes in the GnomAD database, including 15,614 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 0.39 (15614 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 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.519+77778C>T		intron	N/A	NP_001136171.1	Q15700-2
	DLG2	NM_001351274.2		c.555+77778C>T		intron	N/A	NP_001338203.1	A0A994J819
	DLG2	NM_001351275.2		c.552+77778C>T		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.519+77778C>T		intron	N/A	ENSP00000365272.2	Q15700-2
	DLG2	ENST00000398309.6	TSL:1	c.204+77778C>T		intron	N/A	ENSP00000381355.2	Q15700-1
	DLG2	ENST00000532653.5	TSL:1	c.204+77778C>T		intron	N/A	ENSP00000435849.1	B7Z2T4

Frequencies

GnomAD3 genomes AF: 0.389 AC: 58698 AN: 150852 Hom.: 15564 Cov.: 32

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.389 AC: 58798 AN: 150970 Hom.: 15614 Cov.: 32 AF XY: 0.377 AC XY: 27801 AN XY: 73784

African (AFR) AF: 0.759 AC: 31333 AN: 41282

American (AMR) AF: 0.236 AC: 3564 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 881 AN: 3440

East Asian (EAS) AF: 0.229 AC: 1171 AN: 5122

South Asian (SAS) AF: 0.382 AC: 1841 AN: 4814

European-Finnish (FIN) AF: 0.118 AC: 1249 AN: 10598

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17665 AN: 67334

Other (OTH) AF: 0.368 AC: 766 AN: 2084

Alfa AF: 0.302 Hom.: 14179

Bravo AF: 0.410

Asia WGS AF: 0.340 AC: 1183 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.36
PhyloP100		0.0010
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: rs7952143; hg19: chr11-84167835;