Missing gene entry for NM_058195.4 transcript specific exon of CDKN2A

[mhlunimelb]

Apparently older versions of sash included multiple transcripts of CDKN2A in the Gene Somatic CNV Calls Table, but now only
ENST00000304494 is included that does not have a particular exon, and so no gene entry is created when only this exon has a copy number loss.
Would it be possible (at some point) to include both the MANE select ENST00000304494 and the MANE Plus Clinical transcripts ENST00000579755 in the the Gene Somatic CNV Calls Table for this gene?

[qclayssen]

Thanks, do you have an idea, when this change happened ? Is there library I can look at ?

[mhlunimelb]

So L2600127 is the case where this caused an issue.
the region of interest is

name: CDKN2A
id: NM_058195.4

Exon number: 1
chr9:21994139-21994392

So it has a Genome-wide Somatic CNV Segments entry of

Chr	Start	End	CN	CN Min+Maj	Start/End SegSupport	Method	BAF (count)	GC (windowCount)
chr9	21,984,776	23,549,160	0	0+0	DEL-INV	BAF_WEIGHTED	1 (1156)	0.36 (1430)

That results in a CN = 0 for exon 1 of NM_058195.4/ENST00000579755
but only has a minCN of 1 for the UMCCR Gene Somatic CNV Calls table

gene	minCN	maxCN	chrom	start	end	chrBand	onco_or_ts	transcriptID	minMinorAlleleCN	somReg	minReg	minRegStartEnd	minRegSupportStartEndM
CDKN2A	1.0	1.0	chr9	21,967,752	21,995,301	p21.3	tsgene	ENST00000304494	0	1	1	21734916-21984775	DEL-DEL (BAF_WEIGHTED)

[mhlunimelb]

Camilla didn't recall exactly when the change happened, just that sometime last year there were two CDKN2A transcripts.
Peter suggested it might have coincided with a change in purple versions?

[scwatts]

Is it possible the two transcripts were in Umccrise but not sash? I'm struggling to think of differences between recent sash releases that might cause this

[mhlunimelb]

I think it was possibly a lot earlier in 2025 (maybe even 2024) when the curators were first comparing sash and umccrise, but I am not sure.
We are trying to handle it specifically for QCI, but the curators wanted to know if it would be possible to have both transcripts in the cancer report gene table or not? So it doesn't really matter when/if there was a change.

[scwatts]

Got it, and I think I can make sense of that timing. If this isn't pressing perhaps we can chat next week about a solution I have in mind @qclayssen?

[mhlunimelb]

No worries, I warned everyone that we probably wont be able to push any of these fixes to prod until after the wgs accreditation has happened.

[pdiakumis]

For what it's worth this doesn't happen with the OA purple. It keeps the non-canonical ENST00000579755 CDKN2A transcript.

[qclayssen]

If this isn't pressing perhaps we can chat next week about a solution I have in mind @qclayssen?

Happy to discuss that next week @scwatts

[qclayssen]

discussion continue in slack
After change in gene panel commit for ENST00000304494 to be reported

for SBJ07273 (L2600126 / L2600127) :

gene	minCN	maxCN	chrom	start	end	chrBand	onco_or_ts	transcriptID	minMinorAlleleCN	somReg	minReg	minRegStartEnd	minRegSupportStartEnd Method
CDKN2A	0.9675	0.9675	chr9	21967752	21995301	p21.3	tsgene	ENST00000304494	0	1	1	21734916-21984775	DEL-DEL
CDKN2A	0.0444	0.9675	chr9	21967752	21995301	p21.3	tsgene	ENST00000579755	0	2	1	21984776-23549160	DEL-INV

ENST00000579755 is reported in:

• cancer report (s3://pipeline-dev-cache-503977275616-ap-southeast-2/byob-icav2/development/analysis/sash/20260325bg0nqf6g_oob/L2600127_L2600126/L2600127.cancer_report.html)
• purple(s3://pipeline-dev-cache-503977275616-ap-southeast-2/byob-icav2/development/analysis/sash/20260325bg0nqf6g_oob/L2600127_L2600126/cancer_report/cancer_report_tables/purple/L2600127__L2600126_L2600127-purple_cnv_som_gene.tsv.gz) purple_cnv_som_gene.tsv.gz

[scwatts]

@qclayssen I've now made a new release of umccr/gene_panels and a new versioned bundle of the UMCCR workflow reference data:

s3://umccr-refdata-dev/workflow_data/umccr_reference_data/v2--1/

You'll just need to update the relevant version in sash here:

sash/conf/refdata.config

Line 4 in 107cf79

umccr_reference_data = '2--0'