Variant 20-49023200-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.4755+19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,613,152 control chromosomes in the GnomAD database, including 84,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10753 hom., cov: 31)

Exomes 𝑓: 0.31 ( 73829 hom. )

Consequence

ARFGEF2
NM_006420.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.740

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=-0.81).

BP6

Variant 20-49023200-A-G is Benign according to our data. Variant chr20-49023200-A-G is described in ClinVar as [Benign]. Clinvar id is 259980.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-49023200-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ARFGEF2	NM_006420.3 linkuse as main transcript	c.4755+19A>G	intron_variant	ENST00000371917.5	NP_006411.2	Q9Y6D5Q86TH5Q59FR3
ARFGEF2	NM_001410846.1 linkuse as main transcript	c.4752+19A>G	intron_variant		NP_001397775.1
ARFGEF2	XM_047439832.1 linkuse as main transcript	c.4191+19A>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.4755+19A>G		intron_variant		1	NM_006420.3	ENSP00000360985.4		Q9Y6D5

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54850

AN:

151892

Hom.:

10732

Cov.:

show subpopulations

Gnomad AFR

AF:

0.529

Gnomad AMI

AF:

0.477

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.269

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.307

GnomAD3 exomes

AF:

0.297

AC:

74579

AN:

250748

Hom.:

11779

AF XY:

0.295

AC XY:

39982

AN XY:

135546

show subpopulations

Gnomad AFR exome

AF:

0.525

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.155

Gnomad SAS exome

AF:

0.282

Gnomad FIN exome

AF:

0.268

Gnomad NFE exome

AF:

0.315

Gnomad OTH exome

AF:

0.293

GnomAD4 exome

AF:

0.314

AC:

459443

AN:

1461142

Hom.:

73829

Cov.:

AF XY:

0.312

AC XY:

226899

AN XY:

726878

show subpopulations

Gnomad4 AFR exome

AF:

0.524

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.272

Gnomad4 EAS exome

AF:

0.203

Gnomad4 SAS exome

AF:

0.278

Gnomad4 FIN exome

AF:

0.272

Gnomad4 NFE exome

AF:

0.321

Gnomad4 OTH exome

AF:

0.308

GnomAD4 genome

AF:

0.361

AC:

54921

AN:

152010

Hom.:

10753

Cov.:

AF XY:

0.353

AC XY:

26270

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.529

Gnomad4 AMR

AF:

0.263

Gnomad4 ASJ

AF:

0.273

Gnomad4 EAS

AF:

0.189

Gnomad4 SAS

AF:

0.277

Gnomad4 FIN

AF:

0.269

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.311

Alfa

AF:

0.330

Hom.:

1881

Bravo

AF:

0.362

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

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

-0.81

CADD

Benign

0.38

DANN

Benign

0.50

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