BA.2 sublineage with S:K147E, W152R, F157L, I210V, G257S, D339H, G446S, N460K, R493Q (73 seq as of 2022-06-29, mainly India)

[silcn]

Proposal for a sublineage of BA.2
Earliest sequence: 2022-06-02 (India)
Countries detected: India (5 seq, from 3 states)

Defining mutations:
S:K147E, W152R, F157L, I210V, G257S, D339H (mutated from G339D), G446S, N460K, R493Q (reversion)
ORF1a:S1221L, P1640S, N4060S
ORF1b:G662S
E:T11A

Don't think much needs to be said to explain why I'm proposing this. Very recent, long branch with 9 new spike mutations, detection in multiple states that aren't all close together (Maharashtra, Karnataka, Jammu and Kashmir). I expect quite a few people have been monitoring it :)

Usher tree is a bit messy because of some poor quality sequences, particularly the one from Jammu and Kashmir which has multiple artefactual reversions. As a result this lineage is placed on a branch with a couple of Indian sequences with reversions at S:954 (also probably erroneous - apparent reversions at this site seem to crop up a lot in Indian sequences). Despite what the tree shows, the evidence is currently consistent with all 9 S mutations having appeared on the same long branch. As usual, the 2nt mutation at S:339 is mislabelled.

https://nextstrain.org/fetch/github.com/silcn/subtreeAuspice1/raw/main/auspice/subtreeAuspice1_genome_42b02_161030.json?branchLabel=Spike%20mutations&c=gt-S_446&label=nuc%20mutations:C3796T,C3927T,C4586T,C5183T,A12444G,G22577C,G22898A,T22942G,G23040A,A26275G

Genomes:
EPI_ISL_13302209
EPI_ISL_13302252
EPI_ISL_13373059
EPI_ISL_13373170
EPI_ISL_13375776

Edit: cov-spectrum query https://cov-spectrum.org/explore/World/AllSamples/Past6M/variants?variantQuery=%5B6-of%3A+S%3A147E%2C+S%3A152R%2C+S%3A157L%2C+S%3A210V%2C+S%3A257S%2C+S%3A339H%2C+S%3A446S%2C+S%3A460K%2C+ORF1a%3A1221L%2C+ORF1a%3A1640S%2C+ORF1a%3A4060S%5D&
Missing some sequences that only have a month of collection

[ryhisner]

Man, we must be on the same wavelength, Silcn, because I noticed one sequence of this yesterday. I wasn't quite sure what to make of it—whether it was real or not, coming from India, as I don't really have the expertise to judge such things. Excellent spot, mate.

[silcn]

Now found in Germany: EPI_ISL_13378378, EPI_ISL_13378924
And also in Canada: EPI_ISL_13392500
EPI_ISL_13389935 is another Indian sequence, with NNNs covering the locations of all the S mutations but it shares all the non-S mutations.

[silcn]

More Indian sequences: EPI_ISL_13409385, EPI_ISL_13409444, EPI_ISL_13409465

[FedeGueli]

Hi @silcn this morning i found a cluster in Germany with similar mutations (2 out of 8) S:R346K, S:H1101Y, S:460K, S:K147E) and the 493 reversion in Germany:
EPI_ISL_13380484
EPI_ISL_13344896
EPI_ISL_13393217
EPI_ISL_13387937
EPI_ISL_13387015
EPI_ISL_13385893
EPI_ISL_13382835
EPI_ISL_13269776
EPI_ISL_13269123
EPI_ISL_13382561
EPI_ISL_13382506

I cant find them on Usher but maybe you can try to see if they are related or not.

[silcn]

@FedeGueli good spot! Those aren't related - they look like a BA.2/BA.1/BA.2 double-breakpoint recombinant with the first breakpoint between 12880 and 15240, and the second somewhere between 21641 and 21846, i.e. S:27 and S:95 (S:69/70del is present but not S:A67V so not clear whether that bit comes from BA.1 or BA.2). The BA.2 bit in the spike has those extra mutations as you say.

[thomasppeacock]

Although this is still fairly limited in absolute sequence number, the divergent mutation profile, the wide geographical spread, and the rapidness that new sequences have emerged makes me think this should get designated pretty soon to faciliate its monitoring.

[c19850727]

@silcn most of these sequences have T5386G, and 2 of them also have A11537G though. I mean those brought up by @FedeGueli

[silcn]

@c19850727 hmmm, so they do. Doesn't seem too implausible for that to be real if a chronic infection was involved, as suggested by the S mutations? Multiple labs are involved so I doubt it's contamination.

[JosetteSchoenma]

I Sc2rfed the German ones.
I think the 2 breakpoints are between 13195 and 15240 and between 21618 and 21762. Same regions as @silcn suggested, just narrowed the window a bit
But loads of private mutations and all with an extra BA.1 T5386G and 2 with an extra BA.1 A11537G.
Maybe something to keep an eye on and to open up its own issue?

[FedeGueli]

@JosetteSchoenma please do it! you made the analysis i just found it. It is worth flagging it. i will monitor it , at least then we could close the issue if nothing new pops up