chr16-48258634-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_031490.5(LONP2):c.617G>A(p.Ser206Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000125 in 1,602,946 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 (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
LONP2
NM_031490.5 missense
NM_031490.5 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 4.46
Genes affected
LONP2 (HGNC:20598): (lon peptidase 2, peroxisomal) In human, peroxisomes function primarily to catalyze fatty acid beta-oxidation and, as a by-product, produce hydrogen peroxide and superoxide. The protein encoded by this gene is an ATP-dependent protease that likely plays a role in maintaining overall peroxisome homeostasis as well as proteolytically degrading peroxisomal proteins damaged by oxidation. The protein has an N-terminal Lon N substrate recognition domain, an ATPase domain, a proteolytic domain, and, in some isoforms, a C-terminal peroxisome targeting sequence. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2418532).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LONP2 | NM_031490.5 | c.617G>A | p.Ser206Asn | missense_variant | 4/15 | ENST00000285737.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LONP2 | ENST00000285737.9 | c.617G>A | p.Ser206Asn | missense_variant | 4/15 | 1 | NM_031490.5 | P1 | |
LONP2 | ENST00000535754.5 | c.485G>A | p.Ser162Asn | missense_variant | 3/14 | 1 | |||
LONP2 | ENST00000416006.7 | c.485G>A | p.Ser162Asn | missense_variant, NMD_transcript_variant | 3/13 | 2 | |||
LONP2 | ENST00000566755.5 | c.617G>A | p.Ser206Asn | missense_variant, NMD_transcript_variant | 4/14 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152044Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 6.89e-7 AC: 1AN: 1450902Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 721488
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GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152044Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74260
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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 | Feb 17, 2024 | The c.617G>A (p.S206N) alteration is located in exon 4 (coding exon 4) of the LONP2 gene. This alteration results from a G to A substitution at nucleotide position 617, causing the serine (S) at amino acid position 206 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MutPred
Gain of catalytic residue at S206 (P = 0.0066);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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