Variant chr11-83874444-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001142699.3(DLG2):c.1541T>C(p.Leu514Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000872 in 1,601,302 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00089 ( 6 hom. )

Consequence

DLG2
NM_001142699.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.95

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008063883).

BP6

Variant 11-83874444-A-G is Benign according to our data. Variant chr11-83874444-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 252537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 101 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLG2	NM_001142699.3 linkuse as main transcript	c.1541T>C	p.Leu514Pro	missense_variant	16/28	ENST00000376104.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLG2	ENST00000376104.7 linkuse as main transcript	c.1541T>C	p.Leu514Pro	missense_variant	16/28	1	NM_001142699.3		Q15700-2

Frequencies

GnomAD3 genomes

AF:

0.000664

AC:

101

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00664

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00101

AC:

249

AN:

245464

Hom.:

AF XY:

0.00132

AC XY:

176

AN XY:

133312

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000383

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00510

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000693

Gnomad OTH exome

AF:

0.000678

GnomAD4 exome

AF:

0.000894

AC:

1295

AN:

1448984

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

760

AN XY:

720608

show subpopulations

Gnomad4 AFR exome

AF:

0.000331

Gnomad4 AMR exome

AF:

0.000521

Gnomad4 ASJ exome

AF:

0.0000386

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00533

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000648

Gnomad4 OTH exome

AF:

0.000888

GnomAD4 genome

AF:

0.000663

AC:

101

AN:

152318

Hom.:

Cov.:

AF XY:

0.000765

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00664

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000736

Hom.:

Bravo

AF:

0.000468

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000729

AC:

ExAC

AF:

0.00118

AC:

143

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Sep 18, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

.;T;.;.;.;.;T;T;T;T

Eigen

Benign

0.0049

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.073

MetaRNN

Benign

0.0081

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.55

.;N;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.12

N;N;.;.;N;N;N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.15

T;T;.;.;T;T;T;T;T;D

Sift4G

Benign

0.26

T;T;.;.;T;T;T;T;T;T

Polyphen

0.52, 0.32, 0.97, 0.072, 0.10, 0.26, 0.0030

.;P;.;.;B;D;B;B;B;B

Vest4

0.75

MVP

0.89

MPC

2.0

ClinPred

0.046

GERP RS

5.6

Varity_R

0.22

gMVP

0.42

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over