Variant 20-36436163-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001365621.2(DLGAP4):c.1054G>A(p.Asp352Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000278 in 1,596,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

DLGAP4
NM_001365621.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75

Variant links:

Genes affected

DLGAP4 (HGNC:24476): (DLG associated protein 4) The product of this gene is a membrane-associated guanylate kinase found at the postsynaptic density in neuronal cells. It is a signaling molecule that can interact with potassium channels and receptors, as well as other signaling molecules. The protein encoded by this gene can interact with PSD-95 through its guanylate kinase domain and may be involved in clustering PSD-95 in the postsynaptic density region. The encoded protein is one of at least four similar proteins that have been found. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DLGAP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08378735).

BS2

High AC in GnomAd at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP4	NM_001365621.2 linkuse as main transcript	c.1054G>A	p.Asp352Asn	missense_variant	4/13	ENST00000339266.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	UniProt
DLGAP4	ENST00000339266.10 linkuse as main transcript	c.1054G>A	p.Asp352Asn	missense_variant	4/13	5	NM_001365621.2	Q9Y2H0-2
DLGAP4	ENST00000373913.7 linkuse as main transcript	c.1054G>A	p.Asp352Asn	missense_variant	4/13	1		Q9Y2H0-1
DLGAP4	ENST00000373907.6 linkuse as main transcript	c.1054G>A	p.Asp352Asn	missense_variant	3/12	5		Q9Y2H0-2

Frequencies

GnomAD3 genomes

AF:

0.000328

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000235

AC:

AN:

216946

Hom.:

AF XY:

0.000249

AC XY:

AN XY:

120450

show subpopulations

Gnomad AFR exome

AF:

0.0000754

Gnomad AMR exome

AF:

0.0000300

Gnomad ASJ exome

AF:

0.000535

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000810

Gnomad NFE exome

AF:

0.000434

Gnomad OTH exome

AF:

0.000183

GnomAD4 exome

AF:

0.000273

AC:

394

AN:

1444450

Hom.:

Cov.:

AF XY:

0.000315

AC XY:

226

AN XY:

718416

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000927

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000940

Gnomad4 NFE exome

AF:

0.000324

Gnomad4 OTH exome

AF:

0.000117

GnomAD4 genome

AF:

0.000328

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000562

Hom.:

Bravo

AF:

0.000272

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.000235

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2022

The c.1054G>A (p.D352N) alteration is located in exon 3 (coding exon 2) of the DLGAP4 gene. This alteration results from a G to A substitution at nucleotide position 1054, causing the aspartic acid (D) at amino acid position 352 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.74

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.78

M_CAP

Benign

0.010

MetaRNN

Benign

0.084

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.32

N;N;N;N

REVEL

Benign

0.058

Sift

Benign

0.13

T;T;T;T

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.034

B;.;B;.

Vest4

0.23

MVP

0.41

MPC

0.54

ClinPred

0.061

GERP RS

4.2

Varity_R

0.12

gMVP

0.16

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