Variant 18-3534284-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_004746.4(DLGAP1):c.2389C>T(p.Leu797=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0178 in 1,614,218 control chromosomes in the GnomAD database, including 318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.020 ( 38 hom., cov: 32)

Exomes 𝑓: 0.018 ( 280 hom. )

Consequence

DLGAP1
NM_004746.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.01

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=-0.41).

BP6

Variant 18-3534284-G-A is Benign according to our data. Variant chr18-3534284-G-A is described in ClinVar as [Benign]. Clinvar id is 3056064.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0197 (3006/152330) while in subpopulation SAS AF= 0.0294 (142/4834). AF 95% confidence interval is 0.0262. There are 38 homozygotes in gnomad4. There are 1507 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd at 2999 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP1	NM_004746.4 linkuse as main transcript	c.2389C>T	p.Leu797=	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.2389C>T	p.Leu797=	synonymous_variant	10/13	5	NM_004746.4	P1	O14490-1

Frequencies

GnomAD3 genomes

AF:

0.0197

AC:

2999

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0275

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0152

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0289

Gnomad FIN

AF:

0.0261

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0165

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.0166

AC:

4163

AN:

251412

Hom.:

AF XY:

0.0173

AC XY:

2357

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0285

Gnomad AMR exome

AF:

0.00726

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0305

Gnomad FIN exome

AF:

0.0234

Gnomad NFE exome

AF:

0.0157

Gnomad OTH exome

AF:

0.0147

GnomAD4 exome

AF:

0.0176

AC:

25706

AN:

1461888

Hom.:

280

Cov.:

AF XY:

0.0182

AC XY:

13213

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0290

Gnomad4 AMR exome

AF:

0.00803

Gnomad4 ASJ exome

AF:

0.0129

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0296

Gnomad4 FIN exome

AF:

0.0213

Gnomad4 NFE exome

AF:

0.0172

Gnomad4 OTH exome

AF:

0.0182

GnomAD4 genome

AF:

0.0197

AC:

3006

AN:

152330

Hom.:

Cov.:

AF XY:

0.0202

AC XY:

1507

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0276

Gnomad4 AMR

AF:

0.0152

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.000770

Gnomad4 SAS

AF:

0.0294

Gnomad4 FIN

AF:

0.0261

Gnomad4 NFE

AF:

0.0165

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0160

Hom.:

Bravo

AF:

0.0194

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.0162

EpiControl

AF:

0.0161

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

-0.41

Cadd

Benign

Dann

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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