Genetic Variant NM_001142699.3:c.2389C>A (chr11-83471683-G-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001142699.3(DLG2):c.2389C>A(p.Arg797Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00455 in 1,613,058 control chromosomes in the GnomAD database, including 177 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 86 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 91 hom. )

Consequence

DLG2
NM_001142699.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.47

Publications

7 publications found

Variant links:

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

DLG2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 11-83471683-G-T is Benign according to our data. Variant chr11-83471683-G-T is described in ClinVar as [Benign]. Clinvar id is 773011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.47 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3 link	c.2389C>A	p.Arg797Arg	synonymous_variant	Exon 24 of 28	ENST00000376104.7	NP_001136171.1	Q15700-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7 link	c.2389C>A	p.Arg797Arg	synonymous_variant	Exon 24 of 28	1	NM_001142699.3	ENSP00000365272.2		Q15700-2

Frequencies

GnomAD3 genomes

AF:

0.0191

AC:

2906

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00985

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.0244

GnomAD2 exomes

AF:

0.00586

AC:

1457

AN:

248636

AF XY:

0.00463

show subpopulations

Gnomad AFR exome

AF:

0.0615

Gnomad AMR exome

AF:

0.00724

Gnomad ASJ exome

AF:

0.00338

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00151

Gnomad OTH exome

AF:

0.00613

GnomAD4 exome

AF:

0.00303

AC:

4431

AN:

1460944

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

1953

AN XY:

726762

show subpopulations

African (AFR)

AF:

0.0677

AC:

2260

AN:

33402

American (AMR)

AF:

0.00789

AC:

352

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.00337

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.000545

AC:

AN:

86216

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.0189

AC:

109

AN:

5764

European-Non Finnish (NFE)

AF:

0.00105

AC:

1163

AN:

1111410

Other (OTH)

AF:

0.00679

AC:

410

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

215

431

646

862

1077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0191

AC:

2906

AN:

152114

Hom.:

Cov.:

AF XY:

0.0189

AC XY:

1407

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0626

AC:

2596

AN:

41484

American (AMR)

AF:

0.00977

AC:

149

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00124

AC:

AN:

67986

Other (OTH)

AF:

0.0242

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

135

270

406

541

676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00914

Hom.:

Bravo

AF:

0.0217

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.00268

EpiControl

AF:

0.00160

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 31, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

1.5

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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NM_001142699.3:c.2389C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over