Query Regarding HGVS Nomenclature for Copy Number Variants (Amplifications)

[Ketaki Karmalkar]

Respected Sir/Ma'am,

In our laboratory, we perform next-generation sequencing (NGS) using Illumina's short-read technology. A question has arisen regarding the appropriate HGVS nomenclature for reporting duplication copy number variants (CNVs).  

 The HGVS nomenclature guidelines recommend the format xxx_yyy[n] for duplication events inserted directly 3' of the original copy (https://hgvs-nomenclature.org/stable/recommendations/DNA/duplication/). 

Since our CNV calls are derived from NGS data, we are unable to define exact breakpoints. Instead, we report a range of possible breakpoints, as illustrated in the following example:  

chr19:(45409925_45411016)_(45411210_45411789)dup
c.(43+1_44-1)_(236+1_237-1)dup
(Duplication of exon 3)

We have identified two limitations with using the dup suffix in this context:

1. Tandem assumption: The term "duplication" implies that the amplified region is in tandem with the original sequence. Using short-read NGS data alone, we cannot definitively confirm whether the duplicated segment is arranged in tandem.
2. Copy number ambiguity: The dup suffix does not convey the number of copies of the amplified region, which is a value we are able to derive from our NGS data.

To address these limitations, we propose replacing dup with [n], where n represents the copy number determined from NGS data. An example of this proposed notation is as follows:

chr19:(45409925_45411016)_(45411210_45411789) [3]
c.(43+1_44-1)_(236+1_237-1) [3]

(Duplication of exon 3) 

We would like to know whether this annotation approach is acceptable under current HGVS guidelines.

Regards

Ketaki Karmalkar

Scientist-III  

ketaki.k...@strandls.com

[Ketaki Karmalkar]

Hello,

Gentle reminder.

Regards

Ketaki Karmalkar

Scientist-III  

ketaki.k...@strandls.com