Help with SNP Relevance - rs8012(G;G)

[Dan_USAAZ]

I was hoping some of our resident genetic experts(or hobbyists) might be able to look at this SNP and let me know if it warrants follow-up. I got my 23andme done a couple months ago and have been sifting through the details. I do not have a biology background and am new to genetics. High school biology was a long time ago and university took me down a different path.

This particular SNP seemed like it might warrant a deeper look, but I may be completely misinterpreting what I am seeing.

The following is the raw data from 23andme.

rs8012 19 13010520 GG

I have been using Promethease to review the data. I know it may not be the best tool, but it’s affordable.

Genes Affected
GCDH, SYCE2

It appears to me that I am homozygous on two genes for the mutation that causes a metabolic disease (Glutaric acidemia type I).

Many of the other pathogenic SNPs will indicate something like 1.2 times the chance of having some condition. Interesting, but not very definitive. The rs8012(G;G) SNP seems to be suggesting a much greater likelihood of having the disease.

I do not know if I am interpreting this SNP correctly and the possible likelihood of having this metabolic disease. Ultimately I would follow up with a geneticist and/or metabolic specialist, but wanted to first reach out to our knowledgeable members to see if I have completely misunderstood this data or if this is something needing follow up.

Please let me know if any additional information is needed.
Thanks in advance for any input.
Dan

 

[alicec]

G is the wildtype or ancestral allele. You have the normal version of the gene, not the variant - see the dbSNP entry.

 

[Dan_USAAZ]

G is the wildtype or ancestral allele. You have the normal version of the gene, not the variant - see the dbSNP entry.

Thank you @alicec ! Clearly I have a lot to learn.

As mentioned, I used Promethease which linked to SNPedia. SNPedia lists G as the risk allele and A as the common or reference allele.

Am I interpreting the information (common vs risk allele) in SNPedia incorrectly or is SNPedia incorrect?

Also, just noticed that SNPedia appears to be contradicting itself (below) as per the risk allele.

 

[alicec]

SNPedia does sometimes misinterpret things.

The NIH database at dsSNP is a good place to start with info about SNPs. Just enter the rs number in the search by ID box. On the page this brings up you can see under allele which is the ancestral and which is the variant allele along with the population frequency of the minor allele (MAF).

They also give an assessment of the pathogenicity or otherwise of the variant along with links to that assessment (eg ClinVar) as well as links to references showing what is known about the SNP.

Further down the page you will find information about where in the gene the variant lies as well as whether or not the variant has any effect on the protein produced by the gene. This sort of info can be helpful in understanding whether or not the variant is likely to be significant (a change in a non-coding region or a change in the coding region which doesn't change the protein is not in itself likely to have any effect).

Further down still you will see more info on MAF frequencies in different populations.

OMIM.org is another useful site for summarising current knowledge of genetic changes leading to disease states. You can search by genes or diseases.

 

[Dan_USAAZ]

@alicec
Wondelful! Thank you for the help and suggestions!