rs2295029
Positions:
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1
The NM_006420.3(ARFGEF2):c.423+3A>G variant causes a splice donor region, intron change. The variant allele was found at a frequency of 0.00364 in 1,614,124 control chromosomes in the GnomAD database, including 261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0050 ( 27 hom., cov: 31)
Exomes 𝑓: 0.0035 ( 234 hom. )
Consequence
ARFGEF2
NM_006420.3 splice_donor_region, intron
NM_006420.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.9103
1
1
Clinical Significance
Conservation
PhyloP100: 4.44
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -18 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
Variant 20-48951472-A-G is Benign according to our data. Variant chr20-48951472-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 128440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0906 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARFGEF2 | NM_006420.3 | c.423+3A>G | splice_donor_region_variant, intron_variant | ENST00000371917.5 | |||
ARFGEF2 | NM_001410846.1 | c.423+3A>G | splice_donor_region_variant, intron_variant | ||||
ARFGEF2 | XM_047439832.1 | c.-142+3A>G | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARFGEF2 | ENST00000371917.5 | c.423+3A>G | splice_donor_region_variant, intron_variant | 1 | NM_006420.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00499 AC: 759AN: 152174Hom.: 27 Cov.: 31
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GnomAD3 exomes AF: 0.0150 AC: 3780AN: 251400Hom.: 205 AF XY: 0.0109 AC XY: 1481AN XY: 135870
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GnomAD4 exome AF: 0.00350 AC: 5111AN: 1461832Hom.: 234 Cov.: 32 AF XY: 0.00296 AC XY: 2156AN XY: 727226
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GnomAD4 genome ? AF: 0.00500 AC: 761AN: 152292Hom.: 27 Cov.: 31 AF XY: 0.00542 AC XY: 404AN XY: 74478
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jul 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 06, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 05, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 23, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Periventricular heterotopia with microcephaly, autosomal recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at