rs10898278

Variant names:

• chr11-84622198-T-C
• rs10898278
• NM_001142699.3:c.358-87467A>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.358-87467A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,164 control chromosomes in the GnomAD database, including 1,576 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 0.12 (1576 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.703
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 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.358-87467A>G		intron	N/A	NP_001136171.1	Q15700-2
	DLG2	NM_001351274.2		c.394-87467A>G		intron	N/A	NP_001338203.1	A0A994J819
	DLG2	NM_001351275.2		c.394-87470A>G		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.358-87467A>G		intron	N/A	ENSP00000365272.2	Q15700-2
	DLG2	ENST00000398309.6	TSL:1	c.43-87467A>G		intron	N/A	ENSP00000381355.2	Q15700-1
	DLG2	ENST00000532653.5	TSL:1	c.43-87467A>G		intron	N/A	ENSP00000435849.1	B7Z2T4

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18858 AN: 152046 Hom.: 1567 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0706

Gnomad ASJ AF: 0.0622

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0537

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0827

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.124 AC: 18893 AN: 152164 Hom.: 1576 Cov.: 32 AF XY: 0.122 AC XY: 9091 AN XY: 74402

African (AFR) AF: 0.227 AC: 9408 AN: 41478

American (AMR) AF: 0.0704 AC: 1077 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0622 AC: 216 AN: 3470

East Asian (EAS) AF: 0.157 AC: 807 AN: 5154

South Asian (SAS) AF: 0.180 AC: 867 AN: 4820

European-Finnish (FIN) AF: 0.0537 AC: 570 AN: 10616

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0828 AC: 5628 AN: 68010

Other (OTH) AF: 0.122 AC: 258 AN: 2112

Alfa AF: 0.0929 Hom.: 380

Bravo AF: 0.127

Asia WGS AF: 0.178 AC: 620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.70
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: rs10898278; hg19: chr11-84333241;