rs151045115
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2
The NM_006420.3(ARFGEF2):c.3275G>A(p.Arg1092His) variant causes a missense change. The variant allele was found at a frequency of 0.000503 in 1,614,048 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1092S) has been classified as Likely benign.
Frequency
Consequence
NM_006420.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ARFGEF2 | NM_006420.3 | c.3275G>A | p.Arg1092His | missense_variant | 25/39 | ENST00000371917.5 | |
ARFGEF2 | NM_001410846.1 | c.3272G>A | p.Arg1091His | missense_variant | 25/39 | ||
ARFGEF2 | XM_047439832.1 | c.2711G>A | p.Arg904His | missense_variant | 23/37 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARFGEF2 | ENST00000371917.5 | c.3275G>A | p.Arg1092His | missense_variant | 25/39 | 1 | NM_006420.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000500 AC: 76AN: 152042Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00101 AC: 253AN: 251482Hom.: 1 AF XY: 0.000927 AC XY: 126AN XY: 135916
GnomAD4 exome AF: 0.000503 AC: 736AN: 1461888Hom.: 5 Cov.: 34 AF XY: 0.000512 AC XY: 372AN XY: 727242
GnomAD4 genome AF: 0.000499 AC: 76AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 28AN XY: 74388
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 06, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 25, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 29, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 04, 2014 | - - |
Periventricular heterotopia with microcephaly, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at