chr11-83499515-G-T

Variant names:

• chr11-83499515-G-T
• rs1432049
• NM_001142699.3:c.2194-15287C>A

Variant summary

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

The NM_001142699.3(DLG2):​c.2194-15287C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,328 control chromosomes in the GnomAD database, including 9,333 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 0.35 (9333 hom., cov: 30)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322
• Publications: 1 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 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.2194-15287C>A		intron	N/A	NP_001136171.1
	DLG2	NM_001351274.2		c.2230-16217C>A		intron	N/A	NP_001338203.1
	DLG2	NM_001351275.2		c.2227-16217C>A		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.2194-15287C>A		intron	N/A	ENSP00000365272.2
	DLG2	ENST00000398309.6	TSL:1	c.1879-15287C>A		intron	N/A	ENSP00000381355.2
	DLG2	ENST00000532653.5	TSL:1	c.1879-16217C>A		intron	N/A	ENSP00000435849.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 52921 AN: 151212 Hom.: 9342 Cov.: 30

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.379

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

GnomAD4 genome AF: 0.350 AC: 52923 AN: 151328 Hom.: 9333 Cov.: 30 AF XY: 0.346 AC XY: 25583 AN XY: 73896

African (AFR) AF: 0.317 AC: 13069 AN: 41290

American (AMR) AF: 0.306 AC: 4642 AN: 15170

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1222 AN: 3468

East Asian (EAS) AF: 0.390 AC: 1993 AN: 5112

South Asian (SAS) AF: 0.331 AC: 1590 AN: 4798

European-Finnish (FIN) AF: 0.323 AC: 3339 AN: 10352

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25734 AN: 67832

Other (OTH) AF: 0.376 AC: 789 AN: 2100

Alfa AF: 0.248 Hom.: 742

Bravo AF: 0.351

Asia WGS AF: 0.348 AC: 1209 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.6
DANN	Benign	0.49
PhyloP100		0.32
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: rs1432049; hg19: chr11-83210558;