chr11-83578951-A-G

Variant names:

• chr11-83578951-A-G
• rs535809
• NM_001142699.3:c.1941-37093T>C

Variant summary

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

The NM_001142699.3(DLG2):​c.1941-37093T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,014 control chromosomes in the GnomAD database, including 17,919 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 0.48 (17919 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.139
• Publications: 3 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.565 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.1941-37093T>C		intron	N/A	NP_001136171.1	Q15700-2
	DLG2	NM_001351274.2		c.1977-37093T>C		intron	N/A	NP_001338203.1	A0A994J819
	DLG2	NM_001351275.2		c.1974-37093T>C		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.1941-37093T>C		intron	N/A	ENSP00000365272.2	Q15700-2
	DLG2	ENST00000398309.6	TSL:1	c.1626-37093T>C		intron	N/A	ENSP00000381355.2	Q15700-1
	DLG2	ENST00000532653.5	TSL:1	c.1626-37093T>C		intron	N/A	ENSP00000435849.1	B7Z2T4

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72407 AN: 151894 Hom.: 17882 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.350

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.477 AC: 72497 AN: 152014 Hom.: 17919 Cov.: 32 AF XY: 0.479 AC XY: 35598 AN XY: 74298

African (AFR) AF: 0.571 AC: 23688 AN: 41470

American (AMR) AF: 0.573 AC: 8753 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1651 AN: 3470

East Asian (EAS) AF: 0.551 AC: 2852 AN: 5174

South Asian (SAS) AF: 0.496 AC: 2385 AN: 4808

European-Finnish (FIN) AF: 0.369 AC: 3897 AN: 10558

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.411 AC: 27942 AN: 67940

Other (OTH) AF: 0.471 AC: 995 AN: 2112

Alfa AF: 0.439 Hom.: 41813

Bravo AF: 0.495

Asia WGS AF: 0.531 AC: 1847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		-0.14
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: rs535809; hg19: chr11-83289994;