PB0832 - Frequency of VWF single nucleotide variants in a single institution of Argentina.

Background: As in other American countries, Argentineans are the result of the admixture between different migratory groups, mostly from Spain and Italy, and to a lesser extent from Sub-Saharan Africa, and Southeast Asia. This genetic background can produce a high percentage of false positive/negative results due to differences in the genetic composition of our populations.
Currently, there are no data on the frequency of VWF-polymorphisms (SNVs) in Argentine population in EAHAD Coagulation Factor Variant Databases (VWF; Leiden Open Variation Database).

Aims: To analyze the frequency of common VWF-SNVs in our region.

Methods: We analyzed genotypic data of subjects from our institution.
Sixty-seven SNVs within exons 17-28 including exon/intron boundaries were analyzed; 15 were intronic, 52 exonic; 34 were synonymous, 18 non-synonymous. Allele frequencies were calculated for each SNV.

Results: Seven novel SNPs were observed: c.2281+16C>A, c.2442+38G>T, c.2581C>A(p.H861N) and c.2583T>G(p.H861Q), c.3108+34G>A, c.3539-49C>G and c.3539-33G>C.
The most common SNVs with major allele frequency (MAF) < 0.8 were (Table 1):
• intron 17: c.2282-42A>C
• exon 18: c.2365A>G(p.T789A); c.2385T>C(p.Y795=)
• intron 19: c.2546+25T>C
• exon 28: c.4141A>G(p.T1381A); c.4414G>C(p.D1472H); c.4641T>C(p.T1547=)

Conclusion(s): This is the first report of VWF-SNVs frequency in a single institution of Argentina.
In general, the allelic frequency of our population was quite similar to that described in European populations.
However, some discrepancies were observed:
•c.2282-42A>C: our MAF was A, as described in Mancuso´s paper (1989) and ISTH-VWF database, but C in GRCh38.p13 Primary Assembly.
•c.2546+T>C: our MAF: T, as in ISTH-VWF database, but C in Mancuso, and GRCh38.p13 Primary Assembly.
•c.2555G>A(p.R852Q): our MAF was G, as in Mancuso and ISTH-VWF database, but A in GRCh38.p13 Primary Assembly.
•c.3951C>T(p.A1317=): our MAF was C, as in Mancuso and GRCh38.p13 Primary Assembly, but T in ISTH-VWF database.
•c.4141A>G(p.T1381A): our MAF was A, as in GRCh38.p13 Primary Assembly, but G in Mancuso and ISTH database.