Genomic Variant Analysis Report
Budget: £20 – £250 GBP
You have been provided with a patient report, which identified a genetic variant following sequencing of a panel of genes.
Fill out the table provided, detailing the significance of variant and how this aligns with ACMG criteria. You should demonstrate the steps employed to determine the pathogenicity of the variant and cite the resources used.
Child E / Hospital number : HP12345 / Date of Birth :01/11/2019 / Family number : FN12345 / Sex : Male / Date received : 03/07/2024 / NHS number : 123 456 7890 / Sample type : DNA
Referral reason: Diagnostic testing for a panel of genes associated with monogenic hearing loss in Child E, who has bilateral sensorineural hearing loss.
Result: Next generation sequencing has shown that Child E is heterozygous for the MITF variant c.971G>A; p.Arg324Lys.
Gene : MITF
Transcript : NM_001354604.2
DNA variant : c.971G>A
Protein variant : p.R324K
Genomic location (GRCh 38) : Chr3: 69956470
Zygosity : Heterozygous
Resource
How does the gene link to the phenotype of Child E? Details and significance and ACMG criteria required as a response
resources to be used for this Question: OMIM and ClinGen
What is the population frequency of the variant identified? Details and significance and ACMG criteria required as a response
resources to be used for this Question: GnomAD v.4.1.0
Has the variant been reported on clinical databases? Details and significance and ACMG criteria required as a response
resources to be used for this Question: ClinVar
How is the variant predicted to impact the protein? Details and significance and ACMG criteria required as a response
resources to be used for this Question: SpliceAI and Revel
What functional data has been published relevant to the variant in Child E? Details and significance and ACMG criteria required as a response
resources to be used for this Question: Google Scholar, PubMed, GnomAD v.4.1.0
Classification:
Recommendations for further testing?
Fill out the table provided, detailing the significance of variant and how this aligns with ACMG criteria. You should demonstrate the steps employed to determine the pathogenicity of the variant and cite the resources used.
Child E / Hospital number : HP12345 / Date of Birth :01/11/2019 / Family number : FN12345 / Sex : Male / Date received : 03/07/2024 / NHS number : 123 456 7890 / Sample type : DNA
Referral reason: Diagnostic testing for a panel of genes associated with monogenic hearing loss in Child E, who has bilateral sensorineural hearing loss.
Result: Next generation sequencing has shown that Child E is heterozygous for the MITF variant c.971G>A; p.Arg324Lys.
Gene : MITF
Transcript : NM_001354604.2
DNA variant : c.971G>A
Protein variant : p.R324K
Genomic location (GRCh 38) : Chr3: 69956470
Zygosity : Heterozygous
Resource
How does the gene link to the phenotype of Child E? Details and significance and ACMG criteria required as a response
resources to be used for this Question: OMIM and ClinGen
What is the population frequency of the variant identified? Details and significance and ACMG criteria required as a response
resources to be used for this Question: GnomAD v.4.1.0
Has the variant been reported on clinical databases? Details and significance and ACMG criteria required as a response
resources to be used for this Question: ClinVar
How is the variant predicted to impact the protein? Details and significance and ACMG criteria required as a response
resources to be used for this Question: SpliceAI and Revel
What functional data has been published relevant to the variant in Child E? Details and significance and ACMG criteria required as a response
resources to be used for this Question: Google Scholar, PubMed, GnomAD v.4.1.0
Classification:
Recommendations for further testing?