rs2000816

Variant names:

• chr11-84762384-C-T
• rs2000816
• NM_001142699.3:c.358-227653G>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.358-227653G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 151,922 control chromosomes in the GnomAD database, including 18,683 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 0.49 (18683 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• 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

ENSG00000254787 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 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.358-227653G>A		intron	N/A	NP_001136171.1
	DLG2	NM_001351274.2		c.394-227653G>A		intron	N/A	NP_001338203.1
	DLG2	NM_001351275.2		c.394-227656G>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.358-227653G>A		intron	N/A	ENSP00000365272.2
	DLG2	ENST00000398309.6	TSL:1	c.42+160693G>A		intron	N/A	ENSP00000381355.2
	DLG2	ENST00000532653.5	TSL:1	c.42+160693G>A		intron	N/A	ENSP00000435849.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75001 AN: 151804 Hom.: 18670 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.494 AC: 75049 AN: 151922 Hom.: 18683 Cov.: 32 AF XY: 0.500 AC XY: 37101 AN XY: 74252

African (AFR) AF: 0.512 AC: 21226 AN: 41454

American (AMR) AF: 0.480 AC: 7321 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1639 AN: 3468

East Asian (EAS) AF: 0.240 AC: 1242 AN: 5168

South Asian (SAS) AF: 0.506 AC: 2434 AN: 4814

European-Finnish (FIN) AF: 0.580 AC: 6103 AN: 10520

Middle Eastern (MID) AF: 0.524 AC: 151 AN: 288

European-Non Finnish (NFE) AF: 0.490 AC: 33298 AN: 67934

Other (OTH) AF: 0.501 AC: 1055 AN: 2104

Alfa AF: 0.484 Hom.: 31252

Bravo AF: 0.488

Asia WGS AF: 0.375 AC: 1304 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	5.1
DANN	Benign	0.41
PhyloP100		0.18
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: rs2000816; hg19: chr11-84473427;