8-23317021-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_002318.3(LOXL2):c.1564C>T(p.Arg522Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R522H) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOXL2 | NM_002318.3 | c.1564C>T | p.Arg522Cys | missense_variant | 9/14 | ENST00000389131.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXL2 | ENST00000389131.8 | c.1564C>T | p.Arg522Cys | missense_variant | 9/14 | 1 | NM_002318.3 | P1 | |
LOXL2 | ENST00000523833.2 | c.266C>T | p.Pro89Leu | missense_variant | 3/3 | 5 | |||
LOXL2 | ENST00000520617.1 | n.215C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251210Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135808
GnomAD4 exome AF: 0.000134 AC: 196AN: 1461822Hom.: 0 Cov.: 34 AF XY: 0.000131 AC XY: 95AN XY: 727208
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74356
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 23, 2023 | The c.1564C>T (p.R522C) alteration is located in exon 9 (coding exon 8) of the LOXL2 gene. This alteration results from a C to T substitution at nucleotide position 1564, causing the arginine (R) at amino acid position 522 to be replaced by a cysteine (C). 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