Missing genes in PanelApp panel

Hello, me again!

I’m experiencing some missing gene’s in the PanelApp panels loaded into scout. I was testing with scout v4.54 and tried again today with your most recent release v4.56 (and re-loading the PanelApp panels with scout -db load panel --panel-app) and still seem to be experiencing the same thing. Apologies I’m not giving a super tidy reproducible example, just explaining what I’ve observed. If it’s not easily reproduced I’ll spend more time creating a reproducible example 😃

I checked several panels in the scout user interface, (they’re all the most recent versions) here are my observations.

PanelApp panels in scout with all the genes that are found in the green/high confidence list in the PanelApp website:

• Arrhythmogenic cardiomyopathy
• Atypical haemolytic uraemic syndrome
• Arthrogryposis
• Familial hidradenitis suppurativa
• GI tract tumours
• Infantile nystagmus
• Inherited bleeding disorders
• Inherited ovarian cancer (without breast cancer)
• Intracerebral calcification disorders
• Limb girdle muscular dystrophy

PanelApp panels in scout that are missing genes that are found in the green/high confidence list in the PanelApp website:

• CAKUT
• Clefting
• Brain channelopathy
• Mitochondrial disorders

Genes that that were missing from these panels in scout that were “CNV Loss”:

• 17q12 recurrent (RCAD syndrome) region (includes HNF1B) Loss (I’m assuming the HGNC symbol is HNF1B)
• 22q11.2 recurrent (DGS/VCFS) region (proximal, A-B) (includes TBX1) Loss (I’m assuming the HGNC symbol is TBX1)
• 22q11.2 recurrent (DGS/VCFS) region (proximal, A-D) (includes TBX1) Loss ( I’m assuming the HGNC symbol is TBX1)
• Xp11.23 region (includes MAOA and MAOB) Loss (I’m assuming the HGNC symbol is MAOA and MAOB)
• ISCA-37440-Loss 2p21 region (includes PREPL and SLC3A1) Loss (I’m assuming the HGNC symbol is PREPL and SLC3A1)

Genes that that were missing from these panels in scout that were “CNV Gain”:

• 22q11.21 recurrent (Cat eye syndrome) region (includes CECR2) Gain (I’m assuming the HGNC symbol is CECR2)
• 8p23.1 recurrent region (includes GATA4) Gain (I’m assuming the HGNC symbol is GATA4)
• 7q36.3 ZRS (SHH cis-regulatory) duplication region (within LMBR1 intron 5) Gain (I’m assuming the HGNC symbol is LMBR1)

Genes that that were missing from these panels that were “STR”:

• ATN1_CAG (ATN1 is in OMIM and has an associated HGNC gene symbol (ATN1))
• CACNA1A_CAG (CACNA1A is in OMIM and has an associated HGNC gene symbol (CACNA1A))
• CSTB_CCCCGCCCCGCG (CSTB is in OMIM and has an associated HGNC gene symbol (CCSTB))
• TBP_CAG (TBP is in OMIM and has an associated HGNC gene symbol (TBP))

Genes that that were missing from these panels that were other types:

• C5orf42 (C5orf42 is in OMIM and has an associated HGNC gene symbol (CPLANE1))
• C12orf65 (C12orf65 is in OMIM and has an associated HGNC gene symbol (MTRFR))
• C19orf70 (C19orf70 is in OMIM and has an associated HGNC gene symbol (MICOS13))

22q11.21 recurrent (Cat eye syndrome) region (includes CECR2) Gain, 8p23.1 recurrent region (includes GATA4) Gain and 7q36.3 ZRS (SHH cis-regulatory) duplication region (within LMBR1 intron 5) Gain are present in scout and can be accessed by what I assume are their HGNC symbols. For example:

scout --port 27018 -db test-database view hgnc --hgnc-symbol CECR2

My partial output:

#hgnc_id        hgnc_symbol     aliases
1840    CECR2   CECR2, KIAA1740

scout --port 27018 -db test-database view hgnc --hgnc-id 1840

My partial output:

#hgnc_id        hgnc_symbol     aliases
1840    CECR2   CECR2, KIAA1740

ATN1_CAG, CACNA1A_CAG, CSTB_CCCCGCCCCGCG and TBP_CAG are present in scout and can be accessed by what I assume are their HGNC symbols if you drop everything after the underscore. For example:

scout --port 27018 -db test-database view hgnc --hgnc-symbol ATN1_CAG

My partial output:

#hgnc_id        hgnc_symbol     aliases
2022-06-16 17:01:03 leviathan scout.commands.view.hgnc[2619765] INFO No results found

scout --port 27018 -db test-database view hgnc --hgnc-id 3033

My partial output:

#hgnc_id        hgnc_symbol     aliases
3033    ATN1    B37, ATN1, D12S755E, DRPLA

scout --port 27018 -db test-database view hgnc --hgnc-symbol ATN1

My partial output:

#hgnc_id        hgnc_symbol     aliases
3033    ATN1    B37, ATN1, D12S755E, DRPLA

C5orf42, C12orf65 and C19orf70 are present in scout and can be accessed by the HGNC symbols used by PanelApp, their current HGNC symbols and their HGNC id. For example:

scout --port 27018 -db test-database view hgnc --hgnc-symbol C5orf42

My partial output:

#hgnc_id        hgnc_symbol     aliases
25801   CPLANE1 JBTS17, CPLANE1, FLJ13231, Hug, C5orf42

scout --port 27018 -db test-database view hgnc --hgnc-symbol CPLANE1

My partial output:

#hgnc_id        hgnc_symbol     aliases
25801   CPLANE1 JBTS17, Hug, CPLANE1, C5orf42, FLJ13231

scout --port 27018 -db test-database view hgnc --hgnc-id 25801

My partial output:

#hgnc_id        hgnc_symbol     aliases
25801   CPLANE1 JBTS17, Hug, CPLANE1, C5orf42, FLJ13231

It looks like this is where scout is mapping the gene’s in the PanelApp data to the HGNC symbols. My python isn’t great so I haven’t looked much further into the code. Either way it seems like there are some “edge cases” that this function isn’t currently accounting for so they’re just getting considered not present in the database and skipped when loading the PanelApp panels. Another thing to note, I didn’t see any of these “edge case” genes in the reduced HGNC dataset that scout uses for the demo database so these situations might be missed if testing with this reduced dataset.

Hope this is useful, again let me know if you have trouble reproducing this and I’ll spend some time creating a reproducible example 😃

[dnil]

Yep, you are so right. When trying: scout load panel --panel-app --panel-id 112 One can note

2022-06-21 08:09:07 k1315C02VR0WRHTDH.local scout.parse.panel[45277] INFO Parsing panel Mitochondrial disorders
2022-06-21 08:09:07 k1315C02VR0WRHTDH.local scout.parse.panel[45277] WARNING Gene C12orf65 does not exist in database. Skipping gene...
2022-06-21 08:09:07 k1315C02VR0WRHTDH.local scout.parse.panel[45277] WARNING Gene C19orf70 does not exist in database. Skipping gene...

[northwestwitch]

Wicked, tested it out this morning and it looks as though I’m getting all the expected entries in my panels, thanks! 🎉

Thank you for reporting the problem. We are probably going to release a new software version with this patch later today. It will be the last release before the summer holidays this year!