Variant chr20-48988288-G-A 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.2277-16G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 1,606,098 control chromosomes in the GnomAD database, including 64,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5178 hom., cov: 32)

Exomes 𝑓: 0.28 ( 59235 hom. )

Consequence

ARFGEF2
NM_006420.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.170

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:

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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=-0.84).

BP6

Variant 20-48988288-G-A is Benign according to our data. Variant chr20-48988288-G-A is described in ClinVar as [Benign]. Clinvar id is 259979.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-48988288-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
ARFGEF2	NM_006420.3 linkuse as main transcript	c.2277-16G>A	splice_polypyrimidine_tract_variant, intron_variant	ENST00000371917.5	NP_006411.2
ARFGEF2	NM_001410846.1 linkuse as main transcript	c.2274-16G>A	splice_polypyrimidine_tract_variant, intron_variant		NP_001397775.1
ARFGEF2	XM_047439832.1 linkuse as main transcript	c.1713-16G>A	splice_polypyrimidine_tract_variant, 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.2277-16G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_006420.3	ENSP00000360985	P4

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37079

AN:

151804

Hom.:

5172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.363

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.261

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.268

Gnomad OTH

AF:

0.272

GnomAD3 exomes

AF:

0.310

AC:

77345

AN:

249300

Hom.:

13192

AF XY:

0.308

AC XY:

41551

AN XY:

134942

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.271

Gnomad EAS exome

AF:

0.489

Gnomad SAS exome

AF:

0.356

Gnomad FIN exome

AF:

0.265

Gnomad NFE exome

AF:

0.271

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.279

AC:

405859

AN:

1454176

Hom.:

59235

Cov.:

AF XY:

0.282

AC XY:

204155

AN XY:

723816

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.424

Gnomad4 ASJ exome

AF:

0.268

Gnomad4 EAS exome

AF:

0.450

Gnomad4 SAS exome

AF:

0.349

Gnomad4 FIN exome

AF:

0.267

Gnomad4 NFE exome

AF:

0.268

Gnomad4 OTH exome

AF:

0.283

GnomAD4 genome

AF:

0.244

AC:

37096

AN:

151922

Hom.:

5178

Cov.:

AF XY:

0.253

AC XY:

18758

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.364

Gnomad4 ASJ

AF:

0.247

Gnomad4 EAS

AF:

0.472

Gnomad4 SAS

AF:

0.349

Gnomad4 FIN

AF:

0.261

Gnomad4 NFE

AF:

0.268

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.221

Hom.:

1107

Bravo

AF:

0.247

Asia WGS

AF:

0.374

AC:

1301

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
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

- -

Periventricular heterotopia with microcephaly, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.9

DANN

Benign

0.39

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