Variant chr8-1565843-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001346810.2(DLGAP2):c.1391C>A(p.Pro464Gln) variant causes a missense change. The variant allele was found at a frequency of 0.457 in 1,611,828 control chromosomes in the GnomAD database, including 170,570 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15380 hom., cov: 32)

Exomes 𝑓: 0.46 ( 155190 hom. )

Consequence

DLGAP2
NM_001346810.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.47

Variant links:

Genes affected

DLGAP2 (HGNC:2906): (DLG associated protein 2) The product of this gene is a membrane-associated protein that may play a role in synapse organization and signalling in neuronal cells. This gene is biallelically expressed in the brain, however, only the paternal allele is expressed in the testis (PMID:18055845). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jun 2014]

DLGAP2 links:

DLGAP2-AS1 (HGNC:50467): (DLGAP2 antisense RNA 1)

DLGAP2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.1404028E-4).

BP6

Variant 8-1565843-C-A is Benign according to our data. Variant chr8-1565843-C-A is described in ClinVar as [Benign]. Clinvar id is 1272088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP2	NM_001346810.2 link	c.1391C>A	p.Pro464Gln	missense_variant	6/15	ENST00000637795.2	NP_001333739.1	A0A1B0GTN4
DLGAP2-AS1	NR_103863.1 link	n.358-105G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP2	ENST00000637795.2 link	c.1391C>A	p.Pro464Gln	missense_variant	6/15	5	NM_001346810.2	ENSP00000489774.1		A0A1B0GTN4

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67870

AN:

151828

Hom.:

15366

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.483

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.552

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.449

Gnomad OTH

AF:

0.472

GnomAD3 exomes

AF:

0.486

AC:

119394

AN:

245912

Hom.:

29524

AF XY:

0.484

AC XY:

64664

AN XY:

133466

show subpopulations

Gnomad AFR exome

AF:

0.386

Gnomad AMR exome

AF:

0.638

Gnomad ASJ exome

AF:

0.478

Gnomad EAS exome

AF:

0.458

Gnomad SAS exome

AF:

0.553

Gnomad FIN exome

AF:

0.407

Gnomad NFE exome

AF:

0.453

Gnomad OTH exome

AF:

0.501

GnomAD4 exome

AF:

0.458

AC:

668871

AN:

1459882

Hom.:

155190

Cov.:

AF XY:

0.461

AC XY:

335016

AN XY:

726108

show subpopulations

Gnomad4 AFR exome

AF:

0.386

Gnomad4 AMR exome

AF:

0.634

Gnomad4 ASJ exome

AF:

0.483

Gnomad4 EAS exome

AF:

0.478

Gnomad4 SAS exome

AF:

0.557

Gnomad4 FIN exome

AF:

0.405

Gnomad4 NFE exome

AF:

0.446

Gnomad4 OTH exome

AF:

0.468

GnomAD4 genome

AF:

0.447

AC:

67913

AN:

151946

Hom.:

15380

Cov.:

AF XY:

0.451

AC XY:

33458

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.394

Gnomad4 AMR

AF:

0.558

Gnomad4 ASJ

AF:

0.482

Gnomad4 EAS

AF:

0.462

Gnomad4 SAS

AF:

0.553

Gnomad4 FIN

AF:

0.402

Gnomad4 NFE

AF:

0.449

Gnomad4 OTH

AF:

0.475

Alfa

AF:

0.460

Hom.:

35882

Bravo

AF:

0.459

TwinsUK

AF:

0.448

AC:

1660

ALSPAC

AF:

0.439

AC:

1691

ESP6500AA

AF:

0.373

AC:

1604

ESP6500EA

AF:

0.447

AC:

3828

ExAC

AF:

0.477

AC:

57738

Asia WGS

AF:

0.520

AC:

1808

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2019	This variant is associated with the following publications: (PMID: 33343614) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

T;T;T

Eigen

Benign

-0.039

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.41

T;T;T

MetaRNN

Benign

0.00021

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.2

.;M;.

PrimateAI

Uncertain

0.53

REVEL

Benign

0.084

Sift4G

Uncertain

0.040

.;.;D

Polyphen

0.92

.;P;.

Vest4

0.21

MPC

0.097

ClinPred

0.039

GERP RS

4.5

Varity_R

0.11

gMVP

0.40

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