11-84563342-G-T

Variant names:

• chr11-84563342-G-T
• rs948142
• NM_001142699.3:c.358-28611C>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.358-28611C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,052 control chromosomes in the GnomAD database, including 11,035 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 0.36 (11035 hom., cov: 33)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• 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):

• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 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.358-28611C>A		intron	N/A	NP_001136171.1
	DLG2	NM_001351274.2		c.394-28611C>A		intron	N/A	NP_001338203.1
	DLG2	NM_001351275.2		c.394-28614C>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.358-28611C>A		intron	N/A	ENSP00000365272.2
	DLG2	ENST00000398309.6	TSL:1	c.43-28611C>A		intron	N/A	ENSP00000381355.2
	DLG2	ENST00000532653.5	TSL:1	c.43-28611C>A		intron	N/A	ENSP00000435849.1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54996 AN: 151934 Hom.: 11002 Cov.: 33

Gnomad AFR AF: 0.523

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.362 AC: 55089 AN: 152052 Hom.: 11035 Cov.: 33 AF XY: 0.356 AC XY: 26455 AN XY: 74314

African (AFR) AF: 0.523 AC: 21708 AN: 41476

American (AMR) AF: 0.240 AC: 3667 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 848 AN: 3468

East Asian (EAS) AF: 0.187 AC: 967 AN: 5166

South Asian (SAS) AF: 0.485 AC: 2342 AN: 4826

European-Finnish (FIN) AF: 0.203 AC: 2151 AN: 10570

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22399 AN: 67958

Other (OTH) AF: 0.341 AC: 720 AN: 2112

Alfa AF: 0.341 Hom.: 1357

Bravo AF: 0.364

Asia WGS AF: 0.335 AC: 1167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.030
DANN	Benign	0.32
PhyloP100		-2.3
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: rs948142; hg19: chr11-84274385;