rs370805254
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_006420.3(ARFGEF2):c.2814+15G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,614,000 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 0.00028 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 0 hom. )
Consequence
ARFGEF2
NM_006420.3 intron
NM_006420.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.44
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 -7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
Variant 20-48989699-G-C is Benign according to our data. Variant chr20-48989699-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 210233.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000276 (42/152336) while in subpopulation AMR AF= 0.000327 (5/15298). AF 95% confidence interval is 0.000218. There are 0 homozygotes in gnomad4. There are 19 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARFGEF2 | NM_006420.3 | c.2814+15G>C | intron_variant | ENST00000371917.5 | |||
ARFGEF2 | NM_001410846.1 | c.2811+15G>C | intron_variant | ||||
ARFGEF2 | XM_047439832.1 | c.2250+15G>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARFGEF2 | ENST00000371917.5 | c.2814+15G>C | intron_variant | 1 | NM_006420.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000269 AC: 41AN: 152218Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000263 AC: 66AN: 251168Hom.: 0 AF XY: 0.000250 AC XY: 34AN XY: 135754
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GnomAD4 exome AF: 0.000241 AC: 352AN: 1461664Hom.: 0 Cov.: 32 AF XY: 0.000270 AC XY: 196AN XY: 727162
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GnomAD4 genome ? AF: 0.000276 AC: 42AN: 152336Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74488
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 25, 2013 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 15, 2018 | 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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 28, 2023 | - - |
Computational scores
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Name
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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