rs1871748
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 1P and 17B. PP3BP4_StrongBP6_Very_StrongBS1BS2_Supporting
The NM_000098.3(CPT2):āc.1763C>Gā(p.Ser588Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000592 in 1,614,246 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_000098.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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CPT2 | NM_000098.3 | c.1763C>G | p.Ser588Cys | missense_variant | Exon 5 of 5 | ENST00000371486.4 | NP_000089.1 | |
CPT2 | NM_001330589.2 | c.1694C>G | p.Ser565Cys | missense_variant | Exon 5 of 5 | NP_001317518.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00324 AC: 494AN: 152236Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000760 AC: 191AN: 251476Hom.: 1 AF XY: 0.000640 AC XY: 87AN XY: 135908
GnomAD4 exome AF: 0.000316 AC: 462AN: 1461892Hom.: 2 Cov.: 31 AF XY: 0.000315 AC XY: 229AN XY: 727246
GnomAD4 genome AF: 0.00324 AC: 494AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.00322 AC XY: 240AN XY: 74508
ClinVar
Submissions by phenotype
not specified Benign:2
Variant summary: CPT2 c.1763C>G (p.Ser588Cys) results in a non-conservative amino acid change located in the Choline/carnitine acyltransferase domain (IPR039551) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00076 in 251476 control chromosomes, predominantly at a frequency of 0.011 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 7 fold of the estimated maximal expected allele frequency for a pathogenic variant in CPT2 causing Carnitine Palmitoyltransferase II Deficiency phenotype (0.0016). c.1763C>G has been reported in the literature in individuals affected with Carnitine Palmitoyltransferase II Deficiency and Kidney and/or genitourinary disorder, without strong evidence for causality (Rasouly_2019, Isackson_2006). These report(s) do not provide unequivocal conclusions about association of the variant with Carnitine Palmitoyltransferase II Deficiency. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 16996287, 30476936). ClinVar contains an entry for this variant (Variation ID: 203664). Based on the evidence outlined above, the variant was classified as likely benign. -
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Carnitine palmitoyltransferase II deficiency Benign:2
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not provided Benign:2
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Carnitine palmitoyl transferase II deficiency, neonatal form Benign:1
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Carnitine palmitoyl transferase II deficiency, myopathic form Benign:1
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
CPT2-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Encephalopathy, acute, infection-induced, susceptibility to, 4 Benign:1
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Carnitine palmitoyl transferase II deficiency, severe infantile form Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at