8-23317020-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002318.3(LOXL2):c.1565G>A(p.Arg522His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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. R522C) has been classified as Uncertain significance.
Frequency
Consequence
NM_002318.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOXL2 | NM_002318.3 | c.1565G>A | p.Arg522His | missense_variant | 9/14 | ENST00000389131.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXL2 | ENST00000389131.8 | c.1565G>A | p.Arg522His | missense_variant | 9/14 | 1 | NM_002318.3 | P1 | |
LOXL2 | ENST00000523833.2 | c.267G>A | p.Pro89= | synonymous_variant | 3/3 | 5 | |||
LOXL2 | ENST00000520617.1 | n.216G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251126Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135788
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461800Hom.: 0 Cov.: 34 AF XY: 0.0000344 AC XY: 25AN XY: 727194
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152216Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74348
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 10, 2021 | The c.1565G>A (p.R522H) alteration is located in exon 9 (coding exon 8) of the LOXL2 gene. This alteration results from a G to A substitution at nucleotide position 1565, causing the arginine (R) at amino acid position 522 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at