VariantMatcher
VariantMatcher (variantmatcher.org) was developed to connect individuals
(researchers and health care providers) around the globe with interest
in a specific variant. It enables sharing of variant-level and
phenotypic data from participants in research projects for discovery of
novel disease genes including the Baylor-Hopkins Center for Mendelian
Genomics project. VariantMatcher (Wohler et al. 2021) contains the rare
(MAF < 1% in gnomAD), coding (including missense, nonsense,
stop-loss, and splice site variants; synonymous are excluded), single
nucleotide variants identified in 6,235 VCF files (896,847 unique
variants) of affected and unaffected individuals sequenced as part of
multiple projects and their detailed phenotypic information.
To comply with patient privacy and security regulations, users of the
site must register and be approved by site administrators after
verification that the user is a clinician, researcher or health care
providers. Users may upload up to 10 genomic coordinates per day to the
site and are notified of any match. The query format is “chr:coordinate
refAllele > altAllele” (e.g.
chr2:1234567G > T) and is available for genomic builds
hg18, hg19, or hGRCh38. The current VariantMatcher data is on the hg19
build of the human reference assembly. Queries that use hg18 or hg38 are
lifted over to hg19 before the match occurs. Phenotypic features can
also be added, but the match is based only on the genomic location. If
the user adds phenotype information (minimum of three features and
maximum of six), however, and there is a match based on genomic
location, the phenotype information from the matched entries is shared
in the email notifying the users of the match. When there is a match,
both parties are notified by simultaneous emails so that they can choose
to exchange additional information about their cases. If a match is not
made, the queried coordinates can be stored for future matching.
VariantMatcher recently added support for Beacon, a standard for
discovery of genetic variants, developed by the Global Alliance for
Genomics and Health (GA4GH) (Global Alliance for and Health 2016).
Beacon allows users, including anonymous users, to query a database for
the presence of a variant of interest by asking a question of the form
”Do you have information about the following variant?”, to which a
Beacon responds either “yes” or “no”, optionally with additional
aggregate information. Through the Beacon protocol, VariantMatcher was
connected to the Beacon Network (https://beacon-network.org/)
(Fiume et al. 2019). If a user finds out that the variant queried
through the Beacon Network is present in VariantMatcher, they have the
option to create an account in VariantMatcher to obtain further
information about the variant of interest.
As of 1 October 2021, VariantMatcher had 695 submitters from 44
countries. 4,406 variants had been queried and 153 variants matched to
1,248 individuals in VariantMatcher.
To further develop VariantMatcher’s capabilities to support variant
classification and facilitate discovery of disease-causing variants, we
plan to implement additional query capabilities, including: (1) indels;
(2) variants by zygosity state; (3) specific variant with feature(s);
and (4) specific group of variants/gene (e.g. individuals with nonsense
variants in gene X).