rs10501548

Variant names:

• chr11-83795837-T-A
• rs10501548
• NM_001142699.3:c.1723-9045A>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.1723-9045A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0962 in 152,252 control chromosomes in the GnomAD database, including 844 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 0.096 (844 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 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.1723-9045A>T		intron	N/A	NP_001136171.1	Q15700-2
	DLG2	NM_001351274.2		c.1759-9045A>T		intron	N/A	NP_001338203.1	A0A994J819
	DLG2	NM_001351275.2		c.1756-9045A>T		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.1723-9045A>T		intron	N/A	ENSP00000365272.2	Q15700-2
	DLG2	ENST00000398309.6	TSL:1	c.1408-9045A>T		intron	N/A	ENSP00000381355.2	Q15700-1
	DLG2	ENST00000532653.5	TSL:1	c.1408-9045A>T		intron	N/A	ENSP00000435849.1	B7Z2T4

Frequencies

GnomAD3 genomes AF: 0.0963 AC: 14650 AN: 152134 Hom.: 845 Cov.: 32

Gnomad AFR AF: 0.0407

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.0757

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0985

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

GnomAD4 genome AF: 0.0962 AC: 14649 AN: 152252 Hom.: 844 Cov.: 32 AF XY: 0.0986 AC XY: 7341 AN XY: 74438

African (AFR) AF: 0.0407 AC: 1693 AN: 41578

American (AMR) AF: 0.0755 AC: 1155 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3470

East Asian (EAS) AF: 0.101 AC: 525 AN: 5176

South Asian (SAS) AF: 0.168 AC: 810 AN: 4824

European-Finnish (FIN) AF: 0.140 AC: 1479 AN: 10592

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8092 AN: 68002

Other (OTH) AF: 0.0984 AC: 208 AN: 2114

Alfa AF: 0.104 Hom.: 124

Bravo AF: 0.0884

Asia WGS AF: 0.127 AC: 442 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.31
PhyloP100		-0.22
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: rs10501548; hg19: chr11-83506880;