homozygous variants on X and Y choromosome of male patient

[Arvand]

Hello,

I am relatively new to the field of NGS so I will appreciate any help with data analysis.

I have a vcf file sent to me from the center that performed whole-exome sequencing on our patient. This file, however, contains homozygous variants on both X and Y chromosomes of the patient which are not located on PAR regions. So, I am not sure how to explain this and what to make of it.

Sequencing was performed on illumina Miseq and the FASTQ file was analyzed by GATK. Also, the patient's karyotype is normal.

Arvand

[wdecoster]

Most variant callers are not aware of sex chromosomes. So this is what you expect, no? If the variant is homozygous that means all alleles are the same... even when there is only one chromosome. So a homozygous variant on X means just a variant on the one X chromosome, and the same for Y.

[Arvand]

Thank you for your reply.

If this is the case all variants on X and Y chromosome should be reported as homozygous while I just have a few variants with this situation.
To make it more clear, I have just a few variants with allele counts of 2 at some certain positions of X and Y chromosomes outside PAR regions.

[Brian Bushnell]

I guess the real question is, do you have a lot of heterozygous variants outside the PAR? And what kind of coverage and quality do these variants have?

[Arvand]

I have 166 variants on X out of which 158 are homozygous and all of them are outside the PAR regions. read depth is no less than 20 for any of them and quality by depth is also acceptable.
On Y, I have 5 variants, 3 of which are homozygous and outside PAR regions. read depth and quality by depth are also acceptable

I have to add that 3 different callers have detected homozygous variants on X; Naturally, they do not agree on all them though.