chr11-83459914-T-C

Variant names:

• chr11-83459914-T-C
• rs77262037
• NM_001142699.3:c.2832A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001142699.3(DLG2):​c.2832A>G​(p.Gln944Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,580,268 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (56 hom., cov: 33)
  • Exomes 𝑓: 0.0014 (40 hom.)
• Consequence: DLG2 NM_001142699.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.64
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 11-83459914-T-C is Benign according to our data. Variant chr11-83459914-T-C is described in ClinVar as [Benign]. Clinvar id is 782298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.64 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0142 (2168/152318) while in subpopulation AFR AF = 0.0497 (2066/41578). AF 95% confidence interval is 0.0479. There are 56 homozygotes in GnomAd4. There are 997 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 56 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.2832A>G	p.Gln944Gln	synonymous_variant	Exon 28 of 28	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.2832A>G	p.Gln944Gln	synonymous_variant	Exon 28 of 28	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes AF: 0.0142 AC: 2167 AN: 152200 Hom.: 56 Cov.: 33

Gnomad AFR AF: 0.0498

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00365 AC: 905 AN: 248112 AF XY: 0.00260

Gnomad AFR exome AF: 0.0516

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.0000621

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.00136 AC: 1941 AN: 1427950 Hom.: 40 Cov.: 24 AF XY: 0.00111 AC XY: 788 AN XY: 712412

African (AFR) AF: 0.0492 AC: 1615 AN: 32802

American (AMR) AF: 0.00248 AC: 110 AN: 44364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25838

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.0000588 AC: 5 AN: 85038

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53190

Middle Eastern (MID) AF: 0.000527 AC: 3 AN: 5698

European-Non Finnish (NFE) AF: 0.0000407 AC: 44 AN: 1082256

Other (OTH) AF: 0.00275 AC: 163 AN: 59230

GnomAD4 genome AF: 0.0142 AC: 2168 AN: 152318 Hom.: 56 Cov.: 33 AF XY: 0.0134 AC XY: 997 AN XY: 74482

African (AFR) AF: 0.0497 AC: 2066 AN: 41578

American (AMR) AF: 0.00510 AC: 78 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68028

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.00577 Hom.: 17

Bravo AF: 0.0161

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.5
DANN	Benign	0.90
PhyloP100		2.6
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs77262037; hg19: chr11-83170957;