chr11-85440463-T-A

Variant names:

• chr11-85440463-T-A
• rs7116340
• NM_001142699.3:c.41-155098A>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.41-155098A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 152,132 control chromosomes in the GnomAD database, including 44,363 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 0.75 (44363 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• 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):

• 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.865 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.41-155098A>T		intron	N/A	NP_001136171.1
	DLG2	NM_001351274.2		c.152-155098A>T		intron	N/A	NP_001338203.1
	DLG2	NM_001351275.2		c.152-155098A>T		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.41-155098A>T		intron	N/A	ENSP00000365272.2
	DLG2	ENST00000650630.1		c.152-155098A>T		intron	N/A	ENSP00000497771.1
	DLG2	ENST00000706226.1		c.152-155098A>T		intron	N/A	ENSP00000516284.1

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114443 AN: 152016 Hom.: 44372 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.908

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.771

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

GnomAD4 genome AF: 0.752 AC: 114445 AN: 152132 Hom.: 44363 Cov.: 32 AF XY: 0.743 AC XY: 55292 AN XY: 74374

African (AFR) AF: 0.590 AC: 24464 AN: 41488

American (AMR) AF: 0.635 AC: 9701 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2960 AN: 3472

East Asian (EAS) AF: 0.672 AC: 3468 AN: 5158

South Asian (SAS) AF: 0.731 AC: 3522 AN: 4816

European-Finnish (FIN) AF: 0.791 AC: 8378 AN: 10596

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.871 AC: 59242 AN: 68008

Other (OTH) AF: 0.768 AC: 1622 AN: 2112

Alfa AF: 0.805 Hom.: 5926

Bravo AF: 0.733

Asia WGS AF: 0.659 AC: 2290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.6
DANN	Benign	0.52
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7116340; hg19: chr11-85151507;