Variant rs2305309 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_201525.4(ADGRG1):c.1168-20C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,613,080 control chromosomes in the GnomAD database, including 140,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11247 hom., cov: 32)

Exomes 𝑓: 0.42 ( 129079 hom. )

Consequence

ADGRG1
NM_201525.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.45

Variant links:

Genes affected

ADGRG1 (HGNC:4512): (adhesion G protein-coupled receptor G1) This gene encodes a member of the G protein-coupled receptor family and regulates brain cortical patterning. The encoded protein binds specifically to transglutaminase 2, a component of tissue and tumor stroma implicated as an inhibitor of tumor progression. Mutations in this gene are associated with a brain malformation known as bilateral frontoparietal polymicrogyria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ADGRG1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-57657353-C-A is Benign according to our data. Variant chr16-57657353-C-A is described in ClinVar as [Benign]. Clinvar id is 158615.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-57657353-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRG1	NM_201525.4 linkuse as main transcript	c.1168-20C>A		intron_variant		ENST00000562631.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRG1	ENST00000562631.7 linkuse as main transcript	c.1168-20C>A		intron_variant		1	NM_201525.4	P4	Q9Y653-2

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

56145

AN:

152000

Hom.:

11245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.212

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.514

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.226

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.436

Gnomad OTH

AF:

0.400

GnomAD3 exomes

AF:

0.407

AC:

102187

AN:

250974

Hom.:

22220

AF XY:

0.398

AC XY:

54008

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.530

Gnomad ASJ exome

AF:

0.511

Gnomad EAS exome

AF:

0.318

Gnomad SAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.460

Gnomad NFE exome

AF:

0.440

Gnomad OTH exome

AF:

0.424

GnomAD4 exome

AF:

0.415

AC:

606330

AN:

1460966

Hom.:

129079

Cov.:

AF XY:

0.410

AC XY:

298014

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.209

Gnomad4 AMR exome

AF:

0.518

Gnomad4 ASJ exome

AF:

0.507

Gnomad4 EAS exome

AF:

0.314

Gnomad4 SAS exome

AF:

0.236

Gnomad4 FIN exome

AF:

0.460

Gnomad4 NFE exome

AF:

0.431

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.369

AC:

56165

AN:

152114

Hom.:

11247

Cov.:

AF XY:

0.370

AC XY:

27538

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.212

Gnomad4 AMR

AF:

0.445

Gnomad4 ASJ

AF:

0.514

Gnomad4 EAS

AF:

0.319

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.473

Gnomad4 NFE

AF:

0.436

Gnomad4 OTH

AF:

0.397

Alfa

AF:

0.388

Hom.:

6387

Bravo

AF:

0.369

Asia WGS

AF:

0.260

AC:

903

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Bilateral frontoparietal polymicrogyria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.073

DANN

Benign

0.63

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