Variant chr20-36432009-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001365621.2(DLGAP4):c.292A>G(p.Asn98Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

DLGAP4
NM_001365621.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.29

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP4	NM_001365621.2 link	c.292A>G	p.Asn98Asp	missense_variant	3/13	ENST00000339266.10	NP_001352550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DLGAP4	ENST00000339266.10 link	c.292A>G	p.Asn98Asp	missense_variant	3/13	5	NM_001365621.2	ENSP00000341633.5	Q9Y2H0-2
DLGAP4	ENST00000373913.7 link	c.292A>G	p.Asn98Asp	missense_variant	3/13	1		ENSP00000363023.3	Q9Y2H0-1
DLGAP4	ENST00000373907.6 link	c.292A>G	p.Asn98Asp	missense_variant	2/12	5		ENSP00000363014.2	Q9Y2H0-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

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

Nov 11, 2024

The c.292A>G (p.N98D) alteration is located in exon 2 (coding exon 1) of the DLGAP4 gene. This alteration results from a A to G substitution at nucleotide position 292, causing the asparagine (N) at amino acid position 98 to be replaced by an aspartic acid (D). 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

Pathogenic

0.88

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

.;T;.;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

.;D;D;.

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.69

D;D;D;D

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.6

M;M;M;M

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.2

D;D;D;D

REVEL

Benign

0.15

Sift

Uncertain

0.0070

D;D;D;D

Sift4G

Uncertain

0.015

D;D;D;D

Polyphen

0.99

D;.;D;.

Vest4

0.80

MutPred

0.26

Gain of ubiquitination at K96 (P = 0.0497);Gain of ubiquitination at K96 (P = 0.0497);Gain of ubiquitination at K96 (P = 0.0497);Gain of ubiquitination at K96 (P = 0.0497);

MVP

0.73

MPC

1.6

ClinPred

0.97

GERP RS

5.5

Varity_R

0.47

gMVP

0.77

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