Potential BA.1/BA.2 Recombinant Lineage with Likely Breakpoint at NSP3 (38 Seqs in UK as of 2022-03-16)

[c19850727]

Description

Recombinant between: BA.1* & BA.2
Earliest sequence: 2022/2/6 (UK-England)
Most recent sequence: 2022/3/16 (UK-England)
Countries circulating: UK-England
Likely breakpoint: between 6518 and 8392 (NSP3).
Conserved Nuc mutations and AA changes (those in red frames are likely from the donor from the BA.1 side):

Evidence

Usher tree:

https://nextstrain.org/fetch/hgw1.soe.ucsc.edu/trash/ct/subtreeAuspice1_hgw1_2ba44_2dad30.json?c=gt-nuc_875&label=nuc%20mutations:T22792C

Cov-spectrum query: C875T, G14229A, T5386G, A29510C
GISAID query: NS3_T223I, NSP2_L24F, NSP3_K38R, NSP3_L1266I, NSP3_V1069I, NSP4_T492I

Genomes:

EPI_ISL_9839483, EPI_ISL_9839682, EPI_ISL_9872878,
EPI_ISL_9894508, EPI_ISL_10413150, EPI_ISL_10413918,
EPI_ISL_10415682, EPI_ISL_10480052, EPI_ISL_10515444,
EPI_ISL_10537883, EPI_ISL_10641197, EPI_ISL_10688213,
EPI_ISL_10734696, EPI_ISL_10736100, EPI_ISL_10797107,
EPI_ISL_10799679, EPI_ISL_10845598, EPI_ISL_10884842,
EPI_ISL_10885820, EPI_ISL_10885891, EPI_ISL_10885898,
EPI_ISL_10885929, EPI_ISL_10885983, EPI_ISL_10886013,
EPI_ISL_10886093, EPI_ISL_10924779, EPI_ISL_10924994,
EPI_ISL_10930506, EPI_ISL_10932582, EPI_ISL_10938170,
EPI_ISL_10965961, EPI_ISL_10965969, EPI_ISL_10970497,
EPI_ISL_10976194, EPI_ISL_10977401, EPI_ISL_11076474,
EPI_ISL_11092677, EPI_ISL_11092903

[thomasppeacock]

Just been having a look through these - all look legit to me! - only thing is I think the breakpoint might be in NSP3 rather than NSP4 as the sequences are missing the BA.1 lineage definitiong SNP G8393A (which lies at the end of NSP3) but do contain the BA.1-like NSP3 deletion just before this.

[c19850727]

Thanks @thomasppeacock !

[thomasppeacock]

Just confirming UKHSA have had a look over the raw sequences and verified this appears to be a legitimate recombinant

[nfellaby]

Just to support Tom's comment. UKHSA have identified 40 UK samples with a breakpoint at 6941 in the UK sequence data. These were identified with 3Seq (which insists a second breakpoint is annotated, this can be ignored). The other major group of samples listed in this figure are the known recombinant lineage XE

Snipit analysis shows that prior to the break point all these samples predominantly match to the BA.1 reference bases, and post break point, match to the BA.2 reference.

BAM analysis indicates there is no clear indication for contamination in these sequences, see example below for a given sample:

Sample IDs from the pictures are listed here, accurate as of 2022-03-21: EPI_ISL_10413150, EPI_ISL_10413918, EPI_ISL_10415682, EPI_ISL_10480052, EPI_ISL_10515444, EPI_ISL_10525973, EPI_ISL_10532208, EPI_ISL_10535975, EPI_ISL_10537883, EPI_ISL_10578233, EPI_ISL_10641197, EPI_ISL_10688213, EPI_ISL_10734696, EPI_ISL_10736100, EPI_ISL_10797107, EPI_ISL_10799679, EPI_ISL_10845598, EPI_ISL_10884842, EPI_ISL_10885820, EPI_ISL_10885891, EPI_ISL_10885898, EPI_ISL_10885929, EPI_ISL_10885983, EPI_ISL_10886013, EPI_ISL_10886093, EPI_ISL_10924779, EPI_ISL_10924994, EPI_ISL_10930506, EPI_ISL_10932582, EPI_ISL_10938170, EPI_ISL_10965961, EPI_ISL_10965969, EPI_ISL_10970497, EPI_ISL_10976194, EPI_ISL_10977401, EPI_ISL_11223903, EPI_ISL_9839483, EPI_ISL_9839682, EPI_ISL_9872878, EPI_ISL_9894508

[c19850727]

Thanks @thomasppeacock and @nfellaby for the confirmation!

[chrisruis]

Thanks @c19850727 We've added this as XL in v1.2.135