Potential BA.1*/BA.2* Recombinant with Likely Breakpoint at NSP3 (53 Seqs as of 2022-05-11 in Japan, Germany, Slovenia, Canada, UK and US)

[c19850727]

Although this potential recombinant sublineage doesn't meet the minimum criteria of 50 sequences, I thought it's still worth proposing considering it has been found in multiple regions in a relatively short period of time.

Description

Recombinant between: BA.1* & BA.2*
Earliest sequence: 2022/3/13 (Japan ex-Finland)
Most recent sequence: 2022/4/17 (UK-England)
Countries circulating: UK (England), US (MD, CO, NY), Canada (ON), Germany (BW, NW, BB, BE, NI, SN), Japan (ex-Finland)
Likely breakpoint: between 2834 and 4183 (NSP3).
Private mutations: C10507T, C12756T (ORF1a:T4164I), G16020T

Conserved Nuc mutations (those in red frames are likely from the donor from the BA.1 side):

Cov-spectrum query: C10507T, C12756T, G16020T, 9866C
GISAID query: NSP9_T24I, NSP3_K38R, N_S413R, NS3_T223I, -NSP1_S135R

Evidence

Usher tree:

https://nextstrain.org/fetch/genome.ucsc.edu/trash/ct/subtreeAuspice1_genome_2a887_9fc9e0.json?branchLabel=aa%20mutations&c=gt-nuc_10507&label=nuc%20mutations:T9866C,C10507T,C12756T,G16020T

Genomes:

EPI_ISL_11418019, EPI_ISL_11432314, EPI_ISL_11545589, EPI_ISL_11594329, EPI_ISL_11662250, EPI_ISL_11725807, EPI_ISL_11763120, EPI_ISL_11819198, EPI_ISL_12019329, EPI_ISL_12019764, EPI_ISL_12034028, EPI_ISL_12034102, EPI_ISL_12066172, EPI_ISL_12066225, EPI_ISL_12167638, EPI_ISL_12187740, EPI_ISL_12198168, EPI_ISL_12201831, EPI_ISL_12236539, EPI_ISL_12255668, EPI_ISL_12255678, EPI_ISL_12255710, hCoV-19/England/DHSC-CY8UBQJ/2022, hCoV-19/England/DHSC-CY8H6IM/2022

[c19850727]

27 sequences as of 2022-05-01. The 3 new sequences are from Germany-SH.

[c19850727]

41 sequences as of 2022-05-04. 13 of them uploaded a few hours ago from US-CO.

[corneliusroemer]

Very interesting. Looks worth designating due to global spread and recent emergence and potential growth. Global spread points to an unsequenced reservoir.

The 9866C is interesting, because 9866C is very rare outside of South Africa: 70% in South Africa, 1% outside.

@chrisruis I'd recommend this recombinant for designation.

https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants/international-comparison?nucMutations=C10507T%2CC12756T%2CG16020T%2C9866C&

[ktmeaton]

Hi @c19850727, I've missed these samples in my scans, thank you for documenting them! I was wondering how you identified C241T, C2470T, A2832G, C3037T as coming from a BA.1 donor? From the mutation data on cov-spectrum, I'm only able to identify C2470T and A2832G as lineage-defining mutations:

nuc	lineage	freq
C241T	BA.1	0.975
C241T	BA.2	0.939
C241T	BA.3	0.928

nuc	lineage	freq
C2470T	BA.1	0.499
C2470T	BA.2	0.0
C2470T	BA.3	0.066

nuc	lineage	freq
A2832G	BA.1	0.990
A2832G	BA.2	0.0
A2832G	BA.3	0.111

nuc	lineage	freq
C3037T	BA.1	0.992
C3037T	BA.2	0.980
C3037T	BA.3	0.948

And since C2470T to A2832G is such a small segment (362 bp), I've been excluding this as a recombinant. So far, requiring the donor's contribution to be >=1000 bp has helped me weed out false positives. But I might need to revisit that length filter.

Any help you can provide would be greatly appreciated!

[ktmeaton]

Apologies for derailing the discussion, sometimes I need to say things out loud to suddenly realize how and why I'm wrong...

My detection issues were entirely because of C2470T, which has a mutation frequency of 0.499 (JUST under my filter of 0.50).

nuc	lineage	freq
C2470T	BA.1	0.499
C2470T	BA.2	0.0
C2470T	BA.3	0.066

I can reproduce your breakpoints exactly (2834:4183) with sc2rf by reducing the --mutation-threshold to accommodate this:

python3 sc2rf.py pango_designation_issue_591.fasta --unique 1 --mutation-threshold 0.45

Again, apologies for the unnecessary aside! This recombinant looks super clear in terms of parents and breakpoints.

[AngieHinrichs]

C2470T ≈ BA.1.1 which is ~half of BA.1 so there you go. :) (Taxonium (cov2tree.org) has coloring options that are very handy for inspecting mutations in the UCSC/UShER tree. As of this morning, in order to see nucleotide mutations it's necessary to click on the gear icon at the bottom and enable them.)

[c19850727]

51 sequences as of 2022-05-10. The latest batch were from Slovenia, US-NC, US-CO and US-TN.

[c19850727]

53 sequences as of 2022-05-11. The latest 2 sequences were from US-GA and US-FL.

[InfrPopGen]

Thanks for submitting. We've added recombinant lineage XW with 48 newly designated sequences.

[JosetteSchoenma]

XW