8-23298878-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002318.3(LOXL2):c.2203C>T(p.Arg735Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,613,874 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000060 ( 1 hom. )
Consequence
LOXL2
NM_002318.3 missense
NM_002318.3 missense
Scores
5
9
5
Clinical Significance
Conservation
PhyloP100: 2.11
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LOXL2 | NM_002318.3 | c.2203C>T | p.Arg735Cys | missense_variant | 13/14 | ENST00000389131.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LOXL2 | ENST00000389131.8 | c.2203C>T | p.Arg735Cys | missense_variant | 13/14 | 1 | NM_002318.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152196Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251472Hom.: 1 AF XY: 0.0000809 AC XY: 11AN XY: 135908
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GnomAD4 exome AF: 0.0000595 AC: 87AN: 1461678Hom.: 1 Cov.: 30 AF XY: 0.0000825 AC XY: 60AN XY: 727150
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152196Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74348
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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 | Dec 20, 2022 | The c.2203C>T (p.R735C) alteration is located in exon 13 (coding exon 12) of the LOXL2 gene. This alteration results from a C to T substitution at nucleotide position 2203, causing the arginine (R) at amino acid position 735 to be replaced by a cysteine (C). 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
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
T
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0073);
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