11-83471660-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001142699.3(DLG2):c.2412T>C(p.Ser804=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00281 in 1,613,236 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (15 hom.)
• Consequence: DLG2 NM_001142699.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.128

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 11-83471660-A-G is Benign according to our data. Variant chr11-83471660-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 771749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.128 with no splicing effect.
• BS2: High AC in GnomAd at 318 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG2	NM_001142699.3	c.2412T>C	p.Ser804=	synonymous_variant	24/28	ENST00000376104.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG2	ENST00000376104.7	c.2412T>C	p.Ser804=	synonymous_variant	24/28	1	NM_001142699.3

Frequencies

GnomAD3 genomes AF: 0.00209 AC: 318 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00401

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00236 AC: 586 AN: 248614 Hom.: 0 AF XY: 0.00235 AC XY: 317 AN XY: 134878

Gnomad AFR exome AF: 0.000388

Gnomad AMR exome AF: 0.000959

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00186

Gnomad NFE exome AF: 0.00411

Gnomad OTH exome AF: 0.00199

GnomAD4 exome AF: 0.00289 AC: 4216 AN: 1460992 Hom.: 15 Cov.: 30 AF XY: 0.00290 AC XY: 2106 AN XY: 726804

Gnomad4 AFR exome AF: 0.000628

Gnomad4 AMR exome AF: 0.000874

Gnomad4 ASJ exome AF: 0.00337

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00187

Gnomad4 NFE exome AF: 0.00345

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.00209 AC: 318 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.00173 AC XY: 129 AN XY: 74434

Gnomad4 AFR AF: 0.000385

Gnomad4 AMR AF: 0.000590

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000847

Gnomad4 NFE AF: 0.00401

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00351 Hom.: 2

Bravo AF: 0.00222

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00366

EpiControl AF: 0.00409

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2022	DLG2: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	7.6
Dann	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs146333277; hg19: chr11-83182703;