11-83464736-T-C

Variant names:

• chr11-83464736-T-C
• rs891773
• NM_001142699.3:c.2729+1972A>G

Variant summary

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

The NM_001142699.3(DLG2):​c.2729+1972A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,110 control chromosomes in the GnomAD database, including 10,035 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 0.34 (10035 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409
• Publications: 5 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 = 0.529 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.2729+1972A>G		intron	N/A	NP_001136171.1
	DLG2	NM_001351274.2		c.2711+1972A>G		intron	N/A	NP_001338203.1
	DLG2	NM_001351275.2		c.2708+1972A>G		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.2729+1972A>G		intron	N/A	ENSP00000365272.2
	DLG2	ENST00000398309.6	TSL:1	c.2414+1972A>G		intron	N/A	ENSP00000381355.2
	DLG2	ENST00000532653.5	TSL:1	c.2360+1972A>G		intron	N/A	ENSP00000435849.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51826 AN: 151992 Hom.: 10011 Cov.: 32

Gnomad AFR AF: 0.534

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.341 AC: 51893 AN: 152110 Hom.: 10035 Cov.: 32 AF XY: 0.335 AC XY: 24904 AN XY: 74356

African (AFR) AF: 0.535 AC: 22161 AN: 41438

American (AMR) AF: 0.252 AC: 3848 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1040 AN: 3470

East Asian (EAS) AF: 0.260 AC: 1345 AN: 5174

South Asian (SAS) AF: 0.217 AC: 1045 AN: 4826

European-Finnish (FIN) AF: 0.217 AC: 2299 AN: 10602

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18952 AN: 67992

Other (OTH) AF: 0.329 AC: 695 AN: 2112

Alfa AF: 0.278 Hom.: 2582

Bravo AF: 0.356

Asia WGS AF: 0.269 AC: 933 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	1.6
DANN	Benign	0.29
PhyloP100		-0.41
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: rs891773; hg19: chr11-83175779;