Variant 18-3534324-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BS1BS2

The NM_004746.4(DLGAP1):c.2349C>T(p.Ala783=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 1,614,126 control chromosomes in the GnomAD database, including 346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.023 ( 54 hom., cov: 32)

Exomes 𝑓: 0.018 ( 292 hom. )

Consequence

DLGAP1
NM_004746.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.548

Variant links:

Genes affected

DLGAP1 (HGNC:2905): (DLG associated protein 1) Predicted to enable molecular adaptor activity. Predicted to be a structural constituent of postsynaptic density. Predicted to be involved in several processes, including aggresome assembly; regulation of postsynaptic neurotransmitter receptor activity; and regulation of proteasomal protein catabolic process. Predicted to be located in plasma membrane. Predicted to be part of postsynaptic density. Predicted to be active in glutamatergic synapse and postsynaptic density, intracellular component. [provided by Alliance of Genome Resources, Apr 2022]

DLGAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 18-3534324-G-A is Benign according to our data. Variant chr18-3534324-G-A is described in ClinVar as [Benign]. Clinvar id is 3056276.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.548 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0226 (3448/152262) while in subpopulation AFR AF= 0.0377 (1564/41536). AF 95% confidence interval is 0.0361. There are 54 homozygotes in gnomad4. There are 1737 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3448 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP1	NM_004746.4 linkuse as main transcript	c.2349C>T	p.Ala783=	synonymous_variant	10/13	ENST00000315677.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP1	ENST00000315677.8 linkuse as main transcript	c.2349C>T	p.Ala783=	synonymous_variant	10/13	5	NM_004746.4	P1	O14490-1

Frequencies

GnomAD3 genomes

AF:

0.0226

AC:

3438

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0376

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0292

Gnomad FIN

AF:

0.0261

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0164

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.0173

AC:

4358

AN:

251270

Hom.:

AF XY:

0.0180

AC XY:

2445

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.0382

Gnomad AMR exome

AF:

0.00807

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0306

Gnomad FIN exome

AF:

0.0234

Gnomad NFE exome

AF:

0.0158

Gnomad OTH exome

AF:

0.0150

GnomAD4 exome

AF:

0.0178

AC:

26085

AN:

1461864

Hom.:

292

Cov.:

AF XY:

0.0184

AC XY:

13369

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0381

Gnomad4 AMR exome

AF:

0.00885

Gnomad4 ASJ exome

AF:

0.0129

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0297

Gnomad4 FIN exome

AF:

0.0213

Gnomad4 NFE exome

AF:

0.0172

Gnomad4 OTH exome

AF:

0.0190

GnomAD4 genome

AF:

0.0226

AC:

3448

AN:

152262

Hom.:

Cov.:

AF XY:

0.0233

AC XY:

1737

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0377

Gnomad4 AMR

AF:

0.0162

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0297

Gnomad4 FIN

AF:

0.0261

Gnomad4 NFE

AF:

0.0165

Gnomad4 OTH

AF:

0.0217

Alfa

AF:

0.0188

Hom.:

Bravo

AF:

0.0228

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0164

EpiControl

AF:

0.0162

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DLGAP1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 20, 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

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.76

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