Variants

Question 1

c.487A>G/p.N163D

Answer 1

missense variant

Question 2

c.7714-2A>G/IVS11-2A>G

Answer 2

splice site variant

Question 3

c.721C>T/p.R241* or p.Arg241Ter or p.R241X

Answer 3

nonsense variant

Question 4

c.76_78delACT

Answer 4

deletion

Question 5

p.Arg78_Gly79ins23/dup23

Answer 5

duplication or insertion

Question 6

c.112_117delinsTG

Answer 6

indel

Question 7

p.Thr398Profs*10 or p.Thr398fs or p.Thr398ProfsTer10 or p. T398fsX10

Answer 7

frameshift variant

Question 8

Low Impact Variants

Answer 8

silent mutations

Question 9

Moderate or Uncertain Impact Variants

Answer 9

deletions, insertions, indels, missense mutations, splice site mutations

Question 10

High Impact Variants

Answer 10

frameshift mutations, nonsense mutations

Question 11

Variant Interpretation

Answer 11

• takes into account nature of variant, evolutionary conservation, in silico predictors, population frequencies/control databases, literature and disease databases, clinical information and family data

Question 12

Variant Curation

Answer 12

• selecting which variants to report usually in relevant genes/regions, of relevant variant types
• data filtered to narrow down what variants are clinically important and considers affected tissues in which particular transcripts may be present, frequency of variant, disease mechanism

Question 13

Variant Classification

Answer 13

• follows ACMG guidelines regarding which levels of evidence to apply for pathogenicity or benignness
• even with criteria, labs can and do apply evidence differently