rs518143

Variant names:

• chr11-83624721-A-G
• rs518143
• NM_001142699.3:c.1940+8490T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-83624721-A-G
• chr11-83624721-A-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.1940+8490T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,134 control chromosomes in the GnomAD database, including 8,044 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 0.30 (8044 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.866
• Publications: 6 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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.484 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.1940+8490T>C		intron	N/A	NP_001136171.1
	DLG2	NM_001351274.2		c.1976+8490T>C		intron	N/A	NP_001338203.1
	DLG2	NM_001351275.2		c.1973+8490T>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.1940+8490T>C		intron	N/A	ENSP00000365272.2
	DLG2	ENST00000398309.6	TSL:1	c.1625+8490T>C		intron	N/A	ENSP00000381355.2
	DLG2	ENST00000532653.5	TSL:1	c.1625+8490T>C		intron	N/A	ENSP00000435849.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45907 AN: 152016 Hom.: 8031 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.302 AC: 45934 AN: 152134 Hom.: 8044 Cov.: 32 AF XY: 0.306 AC XY: 22792 AN XY: 74376

African (AFR) AF: 0.133 AC: 5523 AN: 41540

American (AMR) AF: 0.464 AC: 7082 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1144 AN: 3466

East Asian (EAS) AF: 0.500 AC: 2582 AN: 5168

South Asian (SAS) AF: 0.311 AC: 1502 AN: 4826

European-Finnish (FIN) AF: 0.337 AC: 3560 AN: 10568

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23623 AN: 67974

Other (OTH) AF: 0.308 AC: 651 AN: 2112

Alfa AF: 0.324 Hom.: 1102

Bravo AF: 0.304

Asia WGS AF: 0.406 AC: 1411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		0.87
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: rs518143; hg19: chr11-83335764;