11-83867472-C-G

Variant names:

• chr11-83867472-C-G
• rs1400306
• NM_001142699.3:c.1565+6948G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142699.3(DLG2):​c.1565+6948G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 151,950 control chromosomes in the GnomAD database, including 33,223 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 0.66 (33223 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148
• Publications: 3 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.1565+6948G>C		intron_variant	Intron 16 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.1565+6948G>C		intron_variant	Intron 16 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100093 AN: 151832 Hom.: 33207 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.809

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.659 AC: 100170 AN: 151950 Hom.: 33223 Cov.: 32 AF XY: 0.658 AC XY: 48813 AN XY: 74218

African (AFR) AF: 0.621 AC: 25729 AN: 41442

American (AMR) AF: 0.634 AC: 9668 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2530 AN: 3472

East Asian (EAS) AF: 0.569 AC: 2941 AN: 5172

South Asian (SAS) AF: 0.613 AC: 2957 AN: 4822

European-Finnish (FIN) AF: 0.644 AC: 6786 AN: 10530

Middle Eastern (MID) AF: 0.818 AC: 239 AN: 292

European-Non Finnish (NFE) AF: 0.694 AC: 47187 AN: 67952

Other (OTH) AF: 0.697 AC: 1470 AN: 2108

Alfa AF: 0.673 Hom.: 4058

Bravo AF: 0.657

Asia WGS AF: 0.620 AC: 2146 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.32
PhyloP100		-0.15
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: rs1400306; hg19: chr11-83578515;