Table 1.

Genetic variants of SARS-CoV-2.

	Genetic variation from reference genome	Common Variants and spatiotemporal, distribution and epidemiological significance	Reference/footnote
1.	2,969 missense mutations, 1,965 synonymous mutations, 484 mutations in the noncoding regions, The most common SNP (single nucleotide polymorphism) was the C to T nucleotide change at the 3,037th position, P4715L in the ORF1ab, D614G mutation in the spike protein; 142 noncoding deletions, 100 in-frame deletions, 11 frameshift deletions; 66 noncoding insertions, two in-frame insertions	5,775 total number of variants reported. D614G found in late January 2020 in China; L84S clades and later D614G/Q57H clades in the USA	(Koyama et al., 2020)
2.	1,516 nucleotide variations; 744 amino acid substitutions; 12 deletion sites in ORF7, ORF8, spike protein, polyprotein ORF1ab (9 deletions spanning NSP1:6, NSP2:1, NSP8:1, NSP15:1), ORF10 (1 deletion), 3’-UTR (2 deletions)	Sequences till March 2020 showed frequency of mutations was the highest in European strains followed by Asian strains North American strains showed the lowest frequency; Case fatality rates were found to be higher in the temperate countries like Spain, Italy, Belgium, France, Netherlands, and England.	(Islam et al., 2020)
3.	10 hotspot mutations in >80% viral isolates worldwide	China, Europe, USA, and India. Mutations at positions 8782 and 28144 with frequencies of 29/99 in sequences from China were found outside China only in samples from USA at moderate frequencies and in samples from India with lower frequencies. The amino acid mutations were predicted to affect replication-related proteins and affect viral secondary structure, virulence, and pathogenicity	(Weber et al., 2020)
4.	716 site mutations; 39 recurrent nonsynonymous mutations including 10 hotspot mutations; mutations were in 6 genes, ORF1ab, spike protein, membrane glycoprotein, nucleocapsid phosphoprotein, ORF3a, and ORF8. The 10 hotspot mutations were D614G mutation at spike protein (43.46%), L84S at ORF8 (23.21%). The gene encoding ORF1ab had 4 mutation hotspots—S5932F of NSP14-exonuclease, M5865V of NSP13-helicase, L3606F of NSP6-transmembrane domain, and T265I of NSP2. Four hotspot mutations in ORF3a (Q57H and G251V) and nucleocapsid phosphoprotein (R203K and G204R) (Laamarti et al., 2020)	Strains circulating in early 2020. USA strains had 44% of total mutations; 24% singleton mutations were specific to the USA. China had 22% of total mutations; France had 4%, Netherlands had 2%; 26 countries showed singleton mutations. Mutations G251V in ORF3a, L84S in ORF8, and S5932F in ORF1ab were found in genomes of all countries except in Austria and in African countries. The mutations F924F, L4715L in orf1ab, D614G in spike protein, and an intergenic variant at position 241 were present in all genomes except in those from Asia. Mutations including two recurrent mutations T265I and Q57H of the ORF3a in Algerian strains were similar to those in European strains. Ten recurrent mutations were shared by European and Dutch genomes. In strains from America, 7 mutations were present in almost all genomes. All genomes from Asia shared 2 mutations at positions 28117 and 28144. Mutations at 1059, 14408, 23403, 25563 and 1397, 11083, 28674, 29742 were shared by African and Australian strains. The number of mutations accumulating in the genome of the virus was increasing with time. In 2020 February, December, and January the average number of mutations were 9.26, 10.59, and 10.34, respectively which changed to 11.34 in March. The first mutations that occurred were in the intergenic region linked to the nucleocapsid phosphoprotein and the orf8 protein. Later, T265I, D614G, and L84S hotspot mutations in orf1ab and Spike proteins arose in late February.	(Laamarti et al., 2020)
5.	Unique mutations: 11 amino acid substitutions, 2 new substitutions I692V downstream of the transmembrane protease serine 2 (TMPRSS2)/furin cleavage site and M1229I within the transmembrane domain; 4 deletions (ΔH69/V70, Y453F, I692V, and M1229I) in addition to D614G; 35 mutations in the spike protein	Lineage B.1.1.298; cluster 5 Emerged in August–September 2020 in North Jutland, Denmark Resistance to neutralization	(Lassaunière et al., 2021)a
	N501Y (asparagine to tyrosine substitution at position 501 in the S gene) and the 69–70del (a deletion of 6 bases coding for histidine and valine at positions 69 and 70 in the S gene) mutations.	“VUI-202012/01,” i.e., “variant under investigation”/20I/501Y.V1/VOC 202012/01 B.1.1.7 or alpha variant in the UK Later spread to 31 other countries including USA, Canada, and India Enhanced transmissibility, with a spreading rate 70% higher than that of wild-type SARS-CoV-2 Escapes neutralization by plasma	(Andreano et al., 2020; Conti et al., 2020; Wang et al., 2020; Callaway, 2021)a,b
6.	Mutation N501Y	Variant 501Y.V2 or 20H/501Y.V2 or B.1.351 or beta variant South Africa and first reported on December 18, 2020 in three provinces of the country and by December 30,2020 spread to four other countries. Higher viral load, increased transmissibility and resistant to neutralization	(Andreano et al., 2020)a,b
7.	Ten mutations in the spike protein (L18F, T20N, P26S, D138Y, R190S, H655Y, T1027I V1176, K417T, E484K, and N501Y). Three mutations (L18F, K417N, E484K) are located in the RBD	P.1 variant Emerged in Brazil in December 2020 Gamma variant or GR/501Y.V3	(Cascella et al., 2021; Rahman et al., 2021)
8.	Spike protein mutations T19R, Δ 156,Δ157-158, L452R, T478K, R158G, D614G, P681R, and D950N; K417N mutation	B.1.617.2 (delta) variant First detected in December 2020 in India and spread to other countries Till now detected in 85 countries 40–60% more transmissible than the Alpha variant (B.1.1.7) Less responsive to vaccines Reduced neutralization	(Lopez Bernal et al., 2021)c
9.	Key amino acid substitutions in spike protein (RBD substitutions in bold type): A67V, del69-70, T95I, del142-144, Y145D, del211, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981F	B.1.1.529 (omicron) First reported by South Africa on December 24, 2021 from samples from Botswana and South Africa Later detected in Europe, Americas, Asia, and Australia Reduced neutralization *501.V2 (Cele et al., 2021), B.1.617.2 (Lopez Bernal et al., 2021), have been found to show lower post-vaccine immune response in certain individuals; for B.1.1.529 it is still uncertain (Collie et al., 2021; Karim and Karim, 2021)	d

^aSARS-CoV-2 Variants (2020) Disease Outbreak News. Available at: https://www.who.int/csr/don/31-december-2020-sars-cov2-variants/en/ (Accessed January 21, 2021).

^bEmerging SARS-CoV-2 Variants. Available at: https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-varian (Accessed January 21, 2021).

^cSARS-CoV-2 Delta (B.1.617.2) variant of concern (VOC) (2021). Available at: https://www.ecdc.europa.eu/en/publications-data/threat-assessment-emergence-and-impact-sars-cov-2-delta-variant (Accessed September 29, 2021).

^dScience Brief Omicron (B.1.1.529) Variant. Available at: https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/scientific-brief-omicron-variant.html#print (Accessed December 30,2021).