rs1945309

Variant names:

• chr11-83732136-G-A
• rs1945309
• NM_001142699.3:c.1825+54554C>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.1825+54554C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,034 control chromosomes in the GnomAD database, including 4,675 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 0.24 (4675 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• Publications: 2 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 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.1825+54554C>T		intron	N/A	NP_001136171.1	Q15700-2
	DLG2	NM_001351274.2		c.1861+54554C>T		intron	N/A	NP_001338203.1	A0A994J819
	DLG2	NM_001351275.2		c.1858+54554C>T		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.1825+54554C>T		intron	N/A	ENSP00000365272.2	Q15700-2
	DLG2	ENST00000398309.6	TSL:1	c.1510+54554C>T		intron	N/A	ENSP00000381355.2	Q15700-1
	DLG2	ENST00000532653.5	TSL:1	c.1510+54554C>T		intron	N/A	ENSP00000435849.1	B7Z2T4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36079 AN: 151916 Hom.: 4662 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.238 AC: 36124 AN: 152034 Hom.: 4675 Cov.: 32 AF XY: 0.240 AC XY: 17812 AN XY: 74326

African (AFR) AF: 0.312 AC: 12951 AN: 41444

American (AMR) AF: 0.143 AC: 2192 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3470

East Asian (EAS) AF: 0.136 AC: 705 AN: 5186

South Asian (SAS) AF: 0.244 AC: 1176 AN: 4824

European-Finnish (FIN) AF: 0.309 AC: 3254 AN: 10534

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.212 AC: 14381 AN: 67976

Other (OTH) AF: 0.213 AC: 449 AN: 2110

Alfa AF: 0.237 Hom.: 1054

Bravo AF: 0.226

Asia WGS AF: 0.201 AC: 704 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.48
PhyloP100		-0.20
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: rs1945309; hg19: chr11-83443179;