rs2295031

chr20-48963810-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0990

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
ARFGEF2	NM_006420.3	c.839-20A>G		intron_variant		ENST00000371917.5
ARFGEF2	NM_001410846.1	c.839-20A>G		intron_variant
ARFGEF2	XM_047439832.1	c.275-20A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARFGEF2	ENST00000371917.5	c.839-20A>G		intron_variant		1	NM_006420.3	P4

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56813 AN: 151710 Hom.: 11484 Cov.: 31

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

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.: 31 AF XY: 0.326 AC XY: 236298 AN XY: 725766

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.: 31 AF XY: 0.366 AC XY: 27162 AN XY: 74188

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	11
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

Other links and lift over

dbSNP: rs2295031; hg19: chr20-47580347; COSMIC: COSV64211863;