Variant chr20-48963810-A-G 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_006420.3(ARFGEF2):c.839-20A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,610,356 control chromosomes in the GnomAD database, including 91,884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11502 hom., cov: 31)

Exomes 𝑓: 0.33 ( 80382 hom. )

Consequence

ARFGEF2
NM_006420.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0990

Variant links:

Genes affected

ARFGEF2 (HGNC:15853): (ADP ribosylation factor guanine nucleotide exchange factor 2) ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP and is involved in Golgi transport. It contains a Sec7 domain, which may be responsible for its guanine-nucleotide exchange activity and also brefeldin A inhibition. [provided by RefSeq, Jul 2008]

ARFGEF2 links:

ARFGEF2 (HGNC:):

ARFGEF2 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=-0.82).

BP6

Variant 20-48963810-A-G is Benign according to our data. Variant chr20-48963810-A-G is described in ClinVar as [Benign]. Clinvar id is 259981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-48963810-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ARFGEF2	NM_006420.3 linkuse as main transcript	c.839-20A>G	intron_variant	ENST00000371917.5	NP_006411.2	Q9Y6D5Q86TH5Q59FR3
ARFGEF2	NM_001410846.1 linkuse as main transcript	c.839-20A>G	intron_variant		NP_001397775.1
ARFGEF2	XM_047439832.1 linkuse as main transcript	c.275-20A>G	intron_variant		XP_047295788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARFGEF2	ENST00000371917.5 linkuse as main transcript	c.839-20A>G		intron_variant		1	NM_006420.3	ENSP00000360985.4		Q9Y6D5

Frequencies

GnomAD3 genomes

AF:

0.374

AC:

56813

AN:

151710

Hom.:

11484

Cov.:

show subpopulations

Gnomad AFR

AF:

0.543

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.276

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.282

Gnomad FIN

AF:

0.279

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.322

GnomAD3 exomes

AF:

0.310

AC:

77691

AN:

250864

Hom.:

12813

AF XY:

0.307

AC XY:

41635

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.538

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.281

Gnomad EAS exome

AF:

0.155

Gnomad SAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.279

Gnomad NFE exome

AF:

0.331

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.328

AC:

478717

AN:

1458528

Hom.:

80382

Cov.:

AF XY:

0.326

AC XY:

236298

AN XY:

725766

show subpopulations

Gnomad4 AFR exome

AF:

0.537

Gnomad4 AMR exome

AF:

0.265

Gnomad4 ASJ exome

AF:

0.283

Gnomad4 EAS exome

AF:

0.203

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.282

Gnomad4 NFE exome

AF:

0.336

Gnomad4 OTH exome

AF:

0.321

GnomAD4 genome

AF:

0.375

AC:

56882

AN:

151828

Hom.:

11502

Cov.:

AF XY:

0.366

AC XY:

27162

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.542

Gnomad4 AMR

AF:

0.276

Gnomad4 ASJ

AF:

0.285

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.282

Gnomad4 FIN

AF:

0.279

Gnomad4 NFE

AF:

0.335

Gnomad4 OTH

AF:

0.327

Alfa

AF:

0.272

Hom.:

1389

Bravo

AF:

0.376

Asia WGS

AF:

0.278

AC:

968

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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