rs41296217
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The ENST00000371917.5(ARFGEF2):c.2940C>T(p.Thr980=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000512 in 1,614,194 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00053 ( 1 hom. )
Consequence
ARFGEF2
ENST00000371917.5 synonymous
ENST00000371917.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.22
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 -15 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 20-48991165-C-T is Benign according to our data. Variant chr20-48991165-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 434283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-4.22 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000328 (50/152308) while in subpopulation NFE AF= 0.000603 (41/68036). AF 95% confidence interval is 0.000457. There are 0 homozygotes in gnomad4. There are 18 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ARFGEF2 | NM_006420.3 | c.2940C>T | p.Thr980= | synonymous_variant | 21/39 | ENST00000371917.5 | NP_006411.2 | |
ARFGEF2 | NM_001410846.1 | c.2937C>T | p.Thr979= | synonymous_variant | 21/39 | NP_001397775.1 | ||
ARFGEF2 | XM_047439832.1 | c.2376C>T | p.Thr792= | synonymous_variant | 19/37 | XP_047295788.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ARFGEF2 | ENST00000371917.5 | c.2940C>T | p.Thr980= | synonymous_variant | 21/39 | 1 | NM_006420.3 | ENSP00000360985 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000335 AC: 51AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000274 AC: 69AN: 251452Hom.: 0 AF XY: 0.000287 AC XY: 39AN XY: 135900
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GnomAD4 exome AF: 0.000531 AC: 776AN: 1461886Hom.: 1 Cov.: 32 AF XY: 0.000520 AC XY: 378AN XY: 727242
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GnomAD4 genome AF: 0.000328 AC: 50AN: 152308Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74476
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 30, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2022 | ARFGEF2: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 02, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 24, 2017 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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