rs750604350
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP6
The NM_000098.3(CPT2):c.1751A>G(p.His584Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,614,142 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H584Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000098.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CPT2 | NM_000098.3 | c.1751A>G | p.His584Arg | missense_variant | 5/5 | ENST00000371486.4 | |
CPT2 | NM_001330589.2 | c.1682A>G | p.His561Arg | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CPT2 | ENST00000371486.4 | c.1751A>G | p.His584Arg | missense_variant | 5/5 | 1 | NM_000098.3 | P1 | |
ENST00000629810.1 | n.104T>C | non_coding_transcript_exon_variant | 1/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251472Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135906
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 727248
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152248Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74384
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 17, 2018 | Variant summary: CPT2 c.1751A>G (p.His584Arg) results in a non-conservative amino acid change located in the Choline/carnitine acyltransferase domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-05 in 246250 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in CPT2 causing Carnitine Palmitoyltransferase II Deficiency (4.1e-05 vs 0.0016), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1751A>G in individuals affected with Carnitine Palmitoyltransferase II Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Carnitine palmitoyltransferase II deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 22, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at