rs756651881
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_006420.3(ARFGEF2):c.2406G>A(p.Arg802Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,358 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
ARFGEF2
NM_006420.3 synonymous
NM_006420.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.605
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 20-48988535-G-A is Benign according to our data. Variant chr20-48988535-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 434280.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-0.605 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARFGEF2 | NM_006420.3 | c.2406G>A | p.Arg802Arg | synonymous_variant | 18/39 | ENST00000371917.5 | NP_006411.2 | |
ARFGEF2 | NM_001410846.1 | c.2403G>A | p.Arg801Arg | synonymous_variant | 18/39 | NP_001397775.1 | ||
ARFGEF2 | XM_047439832.1 | c.1842G>A | p.Arg614Arg | synonymous_variant | 16/37 | XP_047295788.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARFGEF2 | ENST00000371917.5 | c.2406G>A | p.Arg802Arg | synonymous_variant | 18/39 | 1 | NM_006420.3 | ENSP00000360985.4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152048Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000240 AC: 6AN: 250172Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135536
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GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461310Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14AN XY: 726968
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152048Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74266
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 23, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 02, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at