rs797045255
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_006420.3(ARFGEF2):c.1775-9del 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 0.0000155 in 1,611,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
ARFGEF2
NM_006420.3 splice_polypyrimidine_tract, intron
NM_006420.3 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.52
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000395 (6/151998) while in subpopulation NFE AF= 0.0000882 (6/68008). AF 95% confidence interval is 0.0000376. There are 0 homozygotes in gnomad4. There are 3 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARFGEF2 | NM_006420.3 | c.1775-9del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000371917.5 | |||
ARFGEF2 | NM_001410846.1 | c.1772-9del | splice_polypyrimidine_tract_variant, intron_variant | ||||
ARFGEF2 | XM_047439832.1 | c.1211-9del | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARFGEF2 | ENST00000371917.5 | c.1775-9del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006420.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151998Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251148Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135742
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1459844Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 726216
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GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151998Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74252
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 05, 2014 | - - |
Computational scores
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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