rs10501586

Variant names:

• chr11-85045033-T-C
• rs10501586
• NM_001142699.3:c.357+66628A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-85045033-T-C
• chr11-85045033-T-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.357+66628A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 151,988 control chromosomes in the GnomAD database, including 3,555 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 0.20 (3555 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 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.357+66628A>G		intron	N/A	NP_001136171.1
	DLG2	NM_001351274.2		c.393+109523A>G		intron	N/A	NP_001338203.1
	DLG2	NM_001351275.2		c.393+109523A>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.357+66628A>G		intron	N/A	ENSP00000365272.2
	DLG2	ENST00000650630.1		c.468+66628A>G		intron	N/A	ENSP00000497771.1
	DLG2	ENST00000706226.1		c.393+109523A>G		intron	N/A	ENSP00000516284.1

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30924 AN: 151870 Hom.: 3550 Cov.: 32

Gnomad AFR AF: 0.0996

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.0625

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.204 AC: 30933 AN: 151988 Hom.: 3555 Cov.: 32 AF XY: 0.204 AC XY: 15135 AN XY: 74296

African (AFR) AF: 0.0994 AC: 4127 AN: 41504

American (AMR) AF: 0.224 AC: 3415 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1141 AN: 3462

East Asian (EAS) AF: 0.0623 AC: 321 AN: 5152

South Asian (SAS) AF: 0.253 AC: 1216 AN: 4802

European-Finnish (FIN) AF: 0.256 AC: 2703 AN: 10576

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17205 AN: 67928

Other (OTH) AF: 0.217 AC: 458 AN: 2110

Alfa AF: 0.225 Hom.: 1142

Bravo AF: 0.196

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.61
PhyloP100		-0.65
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: rs10501586; hg19: chr11-84756077;