11-83545825-C-T

Variant names:

• chr11-83545825-C-T
• rs2116483
• NM_001142699.3:c.1941-3967G>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.1941-3967G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,894 control chromosomes in the GnomAD database, including 33,433 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 0.66 (33433 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 10 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

LOC107984425 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 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.1941-3967G>A		intron	N/A	NP_001136171.1	Q15700-2
	DLG2	NM_001351274.2		c.1977-3967G>A		intron	N/A	NP_001338203.1	A0A994J819
	DLG2	NM_001351275.2		c.1974-3967G>A		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.1941-3967G>A		intron	N/A	ENSP00000365272.2	Q15700-2
	DLG2	ENST00000398309.6	TSL:1	c.1626-3967G>A		intron	N/A	ENSP00000381355.2	Q15700-1
	DLG2	ENST00000532653.5	TSL:1	c.1626-3967G>A		intron	N/A	ENSP00000435849.1	B7Z2T4

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99921 AN: 151776 Hom.: 33402 Cov.: 32

Gnomad AFR AF: 0.745

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.658

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

GnomAD4 genome AF: 0.658 AC: 99995 AN: 151894 Hom.: 33433 Cov.: 32 AF XY: 0.657 AC XY: 48742 AN XY: 74228

African (AFR) AF: 0.746 AC: 30892 AN: 41426

American (AMR) AF: 0.516 AC: 7871 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2069 AN: 3466

East Asian (EAS) AF: 0.547 AC: 2817 AN: 5150

South Asian (SAS) AF: 0.632 AC: 3042 AN: 4810

European-Finnish (FIN) AF: 0.700 AC: 7388 AN: 10550

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43599 AN: 67926

Other (OTH) AF: 0.653 AC: 1381 AN: 2114

Alfa AF: 0.638 Hom.: 117595

Bravo AF: 0.648

Asia WGS AF: 0.589 AC: 2047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.9
DANN	Benign	0.61
PhyloP100		-0.024
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: rs2116483; hg19: chr11-83256868;