11-85453707-G-T

Position:

• chr11-85453707-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142699.3(DLG2):​c.40+144950C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,020 control chromosomes in the GnomAD database, including 13,867 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 0.42 (13862 hom., cov: 31)
  • Exomes 𝑓: 0.33 (5 hom.)
• Consequence: DLG2 NM_001142699.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45

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]

LOC100421303 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.40+144950C>A		intron_variant		ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.40+144950C>A		intron_variant		1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63898 AN: 151746 Hom.: 13856 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.441

GnomAD4 exome AF: 0.333 AC: 52 AN: 156 Hom.: 5 Cov.: 0 AF XY: 0.321 AC XY: 25 AN XY: 78

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.421 AC: 63907 AN: 151864 Hom.: 13862 Cov.: 31 AF XY: 0.414 AC XY: 30740 AN XY: 74222

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.456

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.442

Alfa AF: 0.468 Hom.: 36614

Bravo AF: 0.418

Asia WGS AF: 0.464 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	2.0
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10898392; hg19: chr11-85164751;