Overview

Clinical Phenotype: Hyperlipoproteinemia Type IIa
Reference Assembly: GRCh37/hg19
Position: Chr19:45412205 G>T
Transcript: NM_000041; ENSG00000130203
dbSNP ID: NA
Coding/Non-Coding: Coding
DNA Change: Substitution
Expected RNA Consequence: Substitution
Expected Protein Consequence: Missense
Codon Change: GGC to TGC
Reference Isoform: APOE Isoform 1
Genomic Region: Exon 4

Findings

This variant was identified in a French patient from a cohort of nearly 6,000 unrelated individuals with primary dyslipidemia (Abou Khalil et al., 2022). The carrier had elevated low-density lipoprotein (LDL) cholesterol in blood and was diagnosed with autosomal dominant hypercholesterolemia, also known as hyperlipoproteinemia type IIa (HLPP2a). They did not carry mutations in the genes most commonly associated with HLPP2a—LDLR, PCSK9, and APOB. They had an APOE3/E4 genotype.

The variant was absent from the gnomAD variant database (gnomAD v3.1.1, Nov 2021).

Biological Effect

The biological effect of this variant is unknown, but computational algorithms SIFT, Mutation Taster, and Provean predicted it is not damaging, although Polyphen2 predicted it is probably damaging. Its PHRED-scaled CADD score was 6.506, well below the commonly used threshold of 20 for predicting a damaging effect (Abou Khalil et al., 2022).

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References

Paper Citations

1. Abou Khalil Y, Marmontel O, Ferrières J, Paillard F, Yelnik C, Carreau V, Charrière S, Bruckert E, Gallo A, Giral P, Philippi A, Bluteau O, Boileau C, Abifadel M, Di-Filippo M, Carrié A, Rabès JP, Varret M. APOE Molecular Spectrum in a French Cohort with Primary Dyslipidemia. Int J Mol Sci. 2022 May 21;23(10) PubMed.

Further Reading

No Available Further Reading