Urgent query - discrepancy between SVs v2.1 & SVs v4.1: missing hemizygotes in the larger dataset

Structural Variation
1

Hello,

This duplication (DMD exons 56-60) is reported in the two datasets with the same size & breakpoints:

GnomAD SVs v2.1 has 1 female carrier, and 6 hemizygotes (which is quite unlikely statistically).
While in SVs v4.1 only 1 female carrier is shown.
The quality in both datasets seems to be good (i.e., filter: PASS, Quality score: 500).

Since this is a duplication in the DMD gene, the occurrences in hemizygous controls might have clinical relevance. Can you please investigate what the reason for the difference can be?

Thank you,
Gyorgy

2

Hi! I asked a similar question about DUP_X_52893 (v2) and DUP_CHRX_19591362 (v4). The gnomAD team responded to the question in this recorded Q&A session that was then uploaded to ClinGen’s YouTube channel. I couldn’t get the transcript, but hopefully this helps!

Question starts at 18:41

3

Thank you! I’ve wathched it. It seems like they have no specific answer, just a generalization. The best approach might be the comparison of the available datasets to rule out potential artefacts.

In this case, the contradiction between the 2 datasets, plus the questionable aspect of 6 hemizygotes in SVs v2.1, makes likely that the true number of occurences is represented by the SVs v4.1 entry.