Anyone work in or understand genetics?

[youarenotkiddingme]

Who could explain a few words or what a report may mean?

Will post the questions if anyone is willing to help but don't want to screenshot as personal medical details.

I may be able to help, I work in genetics.

Thanks so much.

My son had screen for a neuro condition.

It says he is heterozygous for a xxxxx variant of unknown significance in exon 6 of B....2 gene.

Is there an easy way to explain what this means?

We have 2 copies (alleles) of each gene, one allele from mum and one from dad. For some genetic conditions, which are recessive you need to carry two recessive alleles to show the disease. Heterozygous means that he has inherited different alleles of the gene (so doesn’t Have two recessive or two dominant alleles but instead has one recessive and one dominant alleles) for exon (section) 6 of this particular gene

The clinical significance will depend on the gene

Wow thanks. That's made sense!

It's the BSCL2 gene.

Also says the variant not reported in literature or seen in lab.

But been observed at a frequency of 3 out of 207, 000 (Not exact amount but rounded) alleles in the normal control population on gnomAD.

Agree with Veterinari, just wanted to add that as advances are made in sequencing technology a lot of new variants and polymorphisms are being found, it's becoming more frequent to find things that can't be assigned a clinical significance, or at least not yet.

He had the genetic screen as they think he may have the genetic condition.

Hence why they tested this gene (along with 87 others!).

I'm trying to get my head around how he can have a fault on a gene known to be related to the condition and yet possibly that fault has no significance? He still has the signs and symptoms of the genetic condition though!

We have been referred to genetics as suggested by laboratory (written in bold 😂).

But in the meantime I'm kinda stuck feeling we've taken 1 step forward and 2 backwards.

Rather than the variation having no significance, it may be that they just don’t know what the implications of this variation are as it’s rare.

Genetics alone are only part of the puzzle. Epigenetics (the influence of environment on gene expression) and the interplay of genes with other factors are only starting to be understood

Also variant doesn't necessarily equal faulty. You can have copy number variants in genes that don't always affect the gene's biological function.

Thank you.

It also says

It is predicted to result in a conservative substitution of a highly conserved amino acid that is located a recognised functional domain and in silico evolutionary conservation analysis supports a pathogenic role.

Are you able to explain this to me? This whole sentence just confuses me

Thankyou both. You really are helping me get my head around it

Many genes code for amino acids which are the building blocks of the various proteins and enzymes responsible for cellular function

It is predicted that this gene variation will result in the production of a different amino acid (protein building block) than usual. The usual amino acid has a recognised function and is usually highly conserved (unchanged) so a computer model predicts that this change to a different amino acid is likely to result in disease

Do you have an appointment coming up where the significance of these results will be discussed with you OP?

He's we've been referred to genetics as suggested by lab.

Ds was screened for HSP. He has symptoms and everything else (including CP) has been ruled out due to clear MRI.

The results showed a variant on BCSL2 gene which is related to a type of HSP. Except it's not a variant seen before.

It seems from your very helpful description that they predict this variant is causing the issues as know it plays a part but they need to investigate the actual genetics further.

I'm guessing they may want to test my genes too to see if I carry gene if he has one dominant one? We will have an issue in that his father isn't around but these scientists are amazing so I'm sure they'll find a way around it?!

Sorry BSCL2 gene!

Google tells me it plays a part in seipin production.