8-23309875-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_002318.3(LOXL2):c.1673A>C(p.Gln558Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000765 in 1,569,318 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 (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000035 ( 0 hom. )
Consequence
LOXL2
NM_002318.3 missense
NM_002318.3 missense
Scores
4
8
7
Clinical Significance
Conservation
PhyloP100: 6.28
Genes affected
LOXL2 (HGNC:6666): (lysyl oxidase like 2) This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.747
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOXL2 | NM_002318.3 | c.1673A>C | p.Gln558Pro | missense_variant | 10/14 | ENST00000389131.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXL2 | ENST00000389131.8 | c.1673A>C | p.Gln558Pro | missense_variant | 10/14 | 1 | NM_002318.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152224Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000136 AC: 3AN: 220040Hom.: 0 AF XY: 0.00000840 AC XY: 1AN XY: 119114
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GnomAD4 exome AF: 0.00000353 AC: 5AN: 1417094Hom.: 0 Cov.: 34 AF XY: 0.00000285 AC XY: 2AN XY: 701706
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152224Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74364
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 10, 2023 | The c.1673A>C (p.Q558P) alteration is located in exon 10 (coding exon 9) of the LOXL2 gene. This alteration results from a A to C substitution at nucleotide position 1673, causing the glutamine (Q) at amino acid position 558 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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