Week 4 quiz

PVS1 can be applied for which variant types?

• Missense

• Frameshift

• In-frame deletion

• Splice site

• Nonsense

PVS1 can be applied for which of the following variants?

• c.2920G>A; p.(Asp974Asn)

• c.49+6C>T

• c.87-2A>C

• c.2957del; p.(Asn986Alafs*24)

• c.153_155del; p.(Glu51del)

Which of these variants is CANNOT be a true splice site variant?

• c.50+1G>A

• c.50-1G>C

• c.50+2T>A

• c.50-2T>G

Select which scenarios PVS1 should NOT be applied for.

• The disease mechanism is gain of function

• The variant is common in gnomAD

• The variant is absent from gnomAD

• The disease mechanism is loss of function

What can PM4 (protein length changing variant) be applied for?

• An in-frame duplication of one amino acid

• An in-frame deletion of 9 amino acids

• A missense variant

• Whenever a premature stop codon is present, shortening the protein

• A delins variant resulting in no net gain or loss of DNA

Which of these variants is an in-frame deletion?

• c.2927_2929del;

  p.(Ser976del)

• c.2866_3144del;

  p.(His962Aspfs*36)

• c.2926_2927delinsAT;

  p.(Ser976Ile)

• c.2923_2927delinsGACAT;

  p.(Ile975Ser976 delinsAspIle)

Which of these criteria CANNOT ever be applied for a nonsense variant?

• PP3 (computational evidence supports damaging effect)

• PM4 (protein length changing variant)

• BS1 (frequency in population is too high)

• PS2 (de novo with maternity and paternity confirmed)

Which of these criteria can be applied to ANY variant type?

• PP1 (co-segregation with disease)

• PS3 (well established functional studies show a damaging effect)

• PP4 (patient's phenotype highly specific for gene)

• PS4 (prevalence in affecteds increased compared to controls)

• PS1 (same amino acid change as an established pathogenic variant)

Which criteria have Clingen downgraded in strength?

• PM1 (mutational hotspot or functional domain)

• PM2 (absent from gnomAD)

• PP5 (reputable source states variant is pathogenic)

What type of variant is this?

c.4412T>C

p.(*1471Argext*20)

• Frameshift

• Nonsense

• Intronic

• Extension