11-84106317-T-C

Variant names:

• chr11-84106317-T-C
• rs2298830
• NM_001142699.3:c.625-7270A>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.625-7270A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 151,976 control chromosomes in the GnomAD database, including 47,680 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 0.79 (47680 hom., cov: 31)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.863 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.625-7270A>G		intron	N/A	NP_001136171.1	Q15700-2
	DLG2	NM_001351274.2		c.661-7270A>G		intron	N/A	NP_001338203.1	A0A994J819
	DLG2	NM_001351275.2		c.658-7270A>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.625-7270A>G		intron	N/A	ENSP00000365272.2	Q15700-2
	DLG2	ENST00000398309.6	TSL:1	c.310-7270A>G		intron	N/A	ENSP00000381355.2	Q15700-1
	DLG2	ENST00000532653.5	TSL:1	c.310-7270A>G		intron	N/A	ENSP00000435849.1	B7Z2T4

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119438 AN: 151858 Hom.: 47671 Cov.: 31

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.928

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.716

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.786 AC: 119490 AN: 151976 Hom.: 47680 Cov.: 31 AF XY: 0.778 AC XY: 57786 AN XY: 74272

African (AFR) AF: 0.650 AC: 26964 AN: 41454

American (AMR) AF: 0.782 AC: 11930 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.928 AC: 3222 AN: 3472

East Asian (EAS) AF: 0.773 AC: 3990 AN: 5160

South Asian (SAS) AF: 0.824 AC: 3973 AN: 4824

European-Finnish (FIN) AF: 0.716 AC: 7549 AN: 10544

Middle Eastern (MID) AF: 0.901 AC: 265 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59055 AN: 67966

Other (OTH) AF: 0.824 AC: 1733 AN: 2104

Alfa AF: 0.847 Hom.: 179695

Bravo AF: 0.786

Asia WGS AF: 0.789 AC: 2742 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.53
PhyloP100		0.24
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: rs2298830; hg19: chr11-83817360;