Variant 8-1549094-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001346810.2(DLGAP2):c.641G>A(p.Arg214Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,583,196 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 12 hom. )

Consequence

DLGAP2
NM_001346810.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.28

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070053935).

BP6

Variant 8-1549094-G-A is Benign according to our data. Variant chr8-1549094-G-A is described in ClinVar as [Benign]. Clinvar id is 3050378.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP2	NM_001346810.2 linkuse as main transcript	c.641G>A	p.Arg214Lys	missense_variant	5/15	ENST00000637795.2	NP_001333739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP2	ENST00000637795.2 linkuse as main transcript	c.641G>A	p.Arg214Lys	missense_variant	5/15	5	NM_001346810.2	ENSP00000489774
DLGAP2	ENST00000520901.5 linkuse as main transcript	c.452G>A	p.Arg151Lys	missense_variant	1/10	1		ENSP00000430563
DLGAP2	ENST00000421627.7 linkuse as main transcript	c.638G>A	p.Arg213Lys	missense_variant	5/15	5		ENSP00000400258		Q9P1A6-1
DLGAP2	ENST00000612087.1 linkuse as main transcript	c.401G>A	p.Arg134Lys	missense_variant	2/11	5		ENSP00000484215	P1

Frequencies

GnomAD3 genomes

AF:

0.00232

AC:

353

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00300

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00254

AC:

489

AN:

192498

Hom.:

AF XY:

0.00244

AC XY:

258

AN XY:

105722

show subpopulations

Gnomad AFR exome

AF:

0.000286

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.0127

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00103

Gnomad FIN exome

AF:

0.00309

Gnomad NFE exome

AF:

0.00291

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00236

AC:

3373

AN:

1430880

Hom.:

Cov.:

AF XY:

0.00233

AC XY:

1651

AN XY:

709996

show subpopulations

Gnomad4 AFR exome

AF:

0.000273

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.0135

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.00298

Gnomad4 NFE exome

AF:

0.00232

Gnomad4 OTH exome

AF:

0.00279

GnomAD4 genome

AF:

0.00232

AC:

353

AN:

152316

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

160

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00300

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00368

Hom.:

Bravo

AF:

0.00196

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000231

AC:

ESP6500EA

AF:

0.00223

AC:

ExAC

AF:

0.00211

AC:

252

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DLGAP2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;T;T

Eigen

Benign

0.041

Eigen_PC

Benign

0.092

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.89

D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.0070

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.2

.;M;.

MutationTaster

Benign

0.78

PrimateAI

Uncertain

0.73

REVEL

Benign

0.26

Sift4G

Uncertain

0.018

.;.;D

Polyphen

0.058

.;B;.

Vest4

0.63

MVP

0.43

MPC

0.13

ClinPred

0.073

GERP RS

5.6

Varity_R

0.31

gMVP

0.60

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