chr19-3770916-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4BS1_Supporting
The NM_001319074.4(RAX2):c.260G>A(p.Arg87Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000218 in 1,557,406 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R87P) has been classified as Uncertain significance.
Frequency
Consequence
NM_001319074.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAX2 | NM_001319074.4 | c.260G>A | p.Arg87Gln | missense_variant | 3/3 | ENST00000555633.3 | |
RAX2 | NM_032753.4 | c.260G>A | p.Arg87Gln | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAX2 | ENST00000555633.3 | c.260G>A | p.Arg87Gln | missense_variant | 3/3 | 1 | NM_001319074.4 | P1 | |
RAX2 | ENST00000555978.5 | c.260G>A | p.Arg87Gln | missense_variant | 3/3 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000191 AC: 29AN: 152186Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000118 AC: 19AN: 160832Hom.: 0 AF XY: 0.000146 AC XY: 13AN XY: 88880
GnomAD4 exome AF: 0.000221 AC: 310AN: 1405102Hom.: 0 Cov.: 31 AF XY: 0.000217 AC XY: 151AN XY: 695610
GnomAD4 genome ? AF: 0.000190 AC: 29AN: 152304Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74452
ClinVar
Submissions by phenotype
Age related macular degeneration 6 Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 15, 2004 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Aug 20, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 87 of the RAX2 protein (p.Arg87Gln). This variant is present in population databases (rs121908280, gnomAD 0.02%). This missense change has been observed in individual(s) with age-related macular degeneration (PMID: 15028672). ClinVar contains an entry for this variant (Variation ID: 1240). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects RAX2 function (PMID: 15028672). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at