Interpretation of a genetic variant

psaffie
Fri, 08 Dec 2023 16:23:45 +0000
Accessing and Understanding Data

In this post I would like to explain the way to read a genetic laboratory report and its interpretation.

For this purpose I will use an example of a commercial laboratory report:

The genetic variant " c.1561G>A (p.Gly521Arg)" is a specific change in the DNA sequence of the PANK2 gene. Let’s break down each part:

Gene: PANK2: a gene know to produce Neurodegeneration with brain iron accumulation (NBIA). In the new MDS classification this group of conditions were reclassified according to their predominant phenotype. They propose the name DYT-PANK2-(NBIA), as It’s main phenotype is dystonia, but could be accompanied by other movement disorders such as parkinsonism. Actually, it is included under the category of “other diseases with parkinsonism”.

Variant: c.1561G>A: This part describes the specific change in the DNA sequence. The “c.” stands for “coding sequence,” and “1561” is the position of the change in the DNA sequence of the gene. “G>A” indicates that a Guanine (G) is replaced by an Adenine (A) at this position. p.Gly521Arg: This part describes the effect of the DNA change on the protein produced by the gene. The “p.” stands for “protein.” “Gly521Arg” indicates that at position 521 in the protein, the normal Glycine (Gly) is replaced by Arginine (Arg).

Zygosity: heterozygous (one copy of the pathogenic variant), meaning that in a recessive condition, it is not a disease causing genetic variant.

Pathogenicity: This means that the variant is known to cause disease.

If the pathogenicity is not described in the report, it can be found in databases such as ClinVar, which is a freely accessible, public archive of reports of the relationships among human variations and phenotypes.

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