rs7948646

Variant names:

• chr11-85074947-C-A
• rs7948646
• NM_001142699.3:c.357+36714G>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.357+36714G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 151,800 control chromosomes in the GnomAD database, including 4,533 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 0.24 (4533 hom., cov: 32)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.357+36714G>T		intron_variant	Intron 6 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.357+36714G>T		intron_variant	Intron 6 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36043 AN: 151680 Hom.: 4521 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.0449

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.238 AC: 36076 AN: 151800 Hom.: 4533 Cov.: 32 AF XY: 0.237 AC XY: 17608 AN XY: 74202

African (AFR) AF: 0.168 AC: 6954 AN: 41468

American (AMR) AF: 0.270 AC: 4115 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1299 AN: 3460

East Asian (EAS) AF: 0.0450 AC: 231 AN: 5138

South Asian (SAS) AF: 0.271 AC: 1304 AN: 4820

European-Finnish (FIN) AF: 0.263 AC: 2786 AN: 10586

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18533 AN: 67794

Other (OTH) AF: 0.237 AC: 501 AN: 2110

Alfa AF: 0.253 Hom.: 1975

Bravo AF: 0.233

Asia WGS AF: 0.154 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7948646; hg19: chr11-84785991;