11-83615936-C-T

Variant names:

• chr11-83615936-C-T
• rs489567
• NM_001142699.3:c.1940+17275G>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.1940+17275G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 152,124 control chromosomes in the GnomAD database, including 34,879 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 0.67 (34879 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 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.1940+17275G>A		intron	N/A	NP_001136171.1	Q15700-2
	DLG2	NM_001351274.2		c.1976+17275G>A		intron	N/A	NP_001338203.1	A0A994J819
	DLG2	NM_001351275.2		c.1973+17275G>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.1940+17275G>A		intron	N/A	ENSP00000365272.2	Q15700-2
	DLG2	ENST00000398309.6	TSL:1	c.1625+17275G>A		intron	N/A	ENSP00000381355.2	Q15700-1
	DLG2	ENST00000532653.5	TSL:1	c.1625+17275G>A		intron	N/A	ENSP00000435849.1	B7Z2T4

Frequencies

GnomAD3 genomes AF: 0.672 AC: 102109 AN: 152006 Hom.: 34820 Cov.: 32

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.690

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.675

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.672 AC: 102232 AN: 152124 Hom.: 34879 Cov.: 32 AF XY: 0.677 AC XY: 50334 AN XY: 74356

African (AFR) AF: 0.789 AC: 32746 AN: 41526

American (AMR) AF: 0.698 AC: 10663 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2355 AN: 3472

East Asian (EAS) AF: 0.691 AC: 3570 AN: 5168

South Asian (SAS) AF: 0.656 AC: 3170 AN: 4834

European-Finnish (FIN) AF: 0.675 AC: 7128 AN: 10564

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40604 AN: 67962

Other (OTH) AF: 0.646 AC: 1360 AN: 2106

Alfa AF: 0.620 Hom.: 110033

Bravo AF: 0.675

Asia WGS AF: 0.689 AC: 2396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.17
PhyloP100		0.17
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: rs489567; hg19: chr11-83326979;