AG is the result that 23&Me gives for this SNP.
23andme shows that there are two possible alleles at this position, A or G. They then report that your result is AG. So you are heterozygous for this SNP.
23andme doesn't make any comment about which is the ancestral and which is the variant allele. You need to look to other sources to find that out - eg dsSNP.
'Orientation Minus' such that 23&Me has labelled this SNP the 'wrong way' such that it should read CT if it was 'Orientation Positive' (correct way round)?
- 'dbSNP' suggests the unmutated 'default' genotype is CT (which also happens to be what the 23&Me label is when set to 'orientation positive')??
23andme always reports in the plus or forward direction.
dsSNP sometimes reports in the plus orientation and sometimes in the minus. They always indicate which direction is used, so in this case 23andme is telling you that dsSNP is reporting CT in the minus direction for this SNP.
In other words the two results are in complete accord since A always pairs with T and G with C.
This still doesn't tell you which is the ancestral and which is the variant allele, nor does it tell you anything about the significance. dsSNP is a good place to start to find that out.
Here is the entry for that SNP.
So you can see that C (or G in the orientation used by 23andme) is the ancestral allele.
You can see that the variant is pretty common - the minor allele frequency (MAF) is 0.3750 in 4,877 genomes.
The PubMed link will give you research papers that you can look at to evaluate the SNP.
The clinical significance is listed as other, so you need to look further to find out what that means, but it is not listed as a pathogenic SNP.
You can see that it is a missense mutation resulting in a change in the enzyme protein - arginine (R) is replaced by glutamine (Q).
If you look in the map view just below the missense mutation info you will see two little boxes in the vertical band corresponding to the SNP position in the gene. If you hover over these, one will give you a list of publications (though you can find these also in the PubMed link) and the other will give you a link to ClinVar where you will find out what the clinical significance "other" might mean.
This shows it is a risk factor for neural tube defects, giving links to research and to the OMIM page.
So there is clear evidence that the SNP can be an issue for pregnant women, but nothing certain about other conditions.
My notes for this SNP are "protein is thermolabile, activity reduced by 25% +/+; purine synthesis reduced; homozygote assoc with NTD, gastric cancer, schizophrenia, bi-polar; increased requirement choline and methyl folate.
So +/- would have an even smaller effect and undoubtedly would have no consequences for a healthy person.
Whether it has any consequence if other things are disrupting folate metabolism is unknown. My take is that it seems wise to ensure you are getting plenty of folate and choline via diet and maybe supplements.
