11-84907231-C-T

Variant names:

• chr11-84907231-C-T
• rs1940124
• NM_001142699.3:c.357+204430G>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.357+204430G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.879 in 152,176 control chromosomes in the GnomAD database, including 58,936 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 0.88 (58936 hom., cov: 31)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.647
• 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=-0.59).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 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.357+204430G>A		intron	N/A	NP_001136171.1	Q15700-2
	DLG2	NM_001351274.2		c.393+247325G>A		intron	N/A	NP_001338203.1	A0A994J819
	DLG2	NM_001351275.2		c.393+247325G>A		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.357+204430G>A		intron	N/A	ENSP00000365272.2	Q15700-2
	DLG2	ENST00000398309.6	TSL:1	c.42+15846G>A		intron	N/A	ENSP00000381355.2	Q15700-1
	DLG2	ENST00000532653.5	TSL:1	c.42+15846G>A		intron	N/A	ENSP00000435849.1	B7Z2T4

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133664 AN: 152058 Hom.: 58882 Cov.: 31

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.885

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.893

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

GnomAD4 genome AF: 0.879 AC: 133776 AN: 152176 Hom.: 58936 Cov.: 31 AF XY: 0.881 AC XY: 65558 AN XY: 74390

African (AFR) AF: 0.896 AC: 37183 AN: 41504

American (AMR) AF: 0.886 AC: 13538 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2997 AN: 3472

East Asian (EAS) AF: 0.977 AC: 5047 AN: 5168

South Asian (SAS) AF: 0.926 AC: 4460 AN: 4816

European-Finnish (FIN) AF: 0.865 AC: 9167 AN: 10600

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58344 AN: 68016

Other (OTH) AF: 0.895 AC: 1888 AN: 2110

Alfa AF: 0.856 Hom.: 14802

Bravo AF: 0.882

Asia WGS AF: 0.951 AC: 3309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.64
PhyloP100		0.65
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: rs1940124; hg19: chr11-84618275;