An Indian collaborative compendium of genetic variants in BRCA1 and BRCA2 genes for precision oncology and standardised genomic interpretation


Genetic variant databases play an essential role in driving precision oncology. Well annotated databases aid in offering evidence-based classification of variants for clinical actionability - including for diagnosis, therapy guidance and prognosis (e.g. HGMD1, ClinVar2 MarkerDB3, MUSTARD4 etc.). However a number of genetic variants, especially from diverse populations are not well represented in such databases, limiting their utility in clinical decision making. Additionally the multiple standards and criteria utilised by diagnostic laboratories to annotate variants as Pathogenic or Benign make the problem more acute, for clinical interpretation of the reports and further genetic counselling and clinical actionability6.

India is unique in many aspects, with a diverse and stratified population and admixture with major populations across the world , all contributing significantly to the genetic diversity of the population. The recent initiatives aimed at population-scale sequencing like IndiGen have provided a unique opportunity to understand the prevalence of genetic variants in the population.

While a number of laboratories and genetic testing services offer genetic testing/screening for BRCA1 and BRCA2 genetic variants, the lack of a uniform system followed across the laboratories for the interpretation of the pathogenicity of genetic variants has limited the clinical actionability of variants in clinical settings. Such non-standard approaches have also resulted in inter-clinician and inter-lab differences in interpretation including sometimes conflicting interpretations of genetic variants and their pathogenicity. The ACMG & AMP joint guidelines for the interpretation of pathogenicity of genetic variants is a globally followed system now in place, but due to the fact that the interpretation is time-consuming, tedious and requires careful evaluation of published evidence, is not followed widely in India.

What and Why ?

This programme envisages the creation of a genetic variant compendium for BRCA1 and BRCA2 derived from the clinical reports from India, which would be re-classified according to the ACMG & AMP joint guidelines and made available for clinicians for ready reference. Additionally, since newer evidence has been emerging in this area, additional advancements and consequence changes in interpretation, especially for the variants of uncertain significance (VUS) would also be updated on the resource for ready reference.

Additionally, the exhaustive compendium of variants from Indian population would enable genetic epidemiology of BRCA1 and BRCA2 variants in Indian populations with impact in public health endeavours enabling swift, accurate diagnosis and help in genetic counselling.

Participating in the collection

Clinical collaborators are encouraged to participate in this endeavour. Collaborators are expected to share genetic variants and classification on pathogenicity (without any personal or identifiable information on the patient) in a predetermined proforma. They could also share entries already submitted to a public database like ClinVar or dbSNP .

For clinicians interested in learning classification of pathogenicity of variants as per the ACMG & AMP Guidelines may also see the GVACI Course

Clinicians contributing towards the endeavour would be duly credited / acknowledged depending on the contributions made to the database.

The compendium of variants and their pathogenicity would be made available to all participants without restrictions along with the reassessed classifications.

Clinicians interested in the endeavour could let us know by providing information at so we could reach out to you with details


Dr. Vinod Scaria, CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB) at

Dr Anu R.I , MVR Cancer Centre for more details.

Genomic Variant Analysis and Clinical Interpretation Course

You could learn how to systematically compile evidence and assess pathogenicity of variants This 16 weeks online course providing hands-on exposure to genomic variant analysis and clinical interpretation of germline variants.

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