Background CSER Study Overview Reanalysis Study Design ...
Reanalysis of Exomes with No Results or Variants of Uncertain Significance Leads to New Diagnoses Susan M. Hia\1, Michelle D. Amaral1, Gregory S. Barsh1, E. Mar;na Bebin2, Kevin M. Bowling1, Kyle B. Brothers3, Kelly M. East1, Candice R. Finnila1, David E. Gray1, Whitley V. Kelley1, Neil E. Lamb1, Edward J. Lose2, Richard M. Myers1, Carla A. Rich3, Shirley B. Simmons2, Jana S. Whi\le1 , Gregory M. Cooper1
1HudsonAlpha Ins;tute for Biotechnology, 2University of Alabama at Birmingham, 3University of Louisville
Background
Reanalysis Study Design A
140
A L I G N M E N T / G E N O T Y P I N G / A N N O T A T I O N
Unaffected!
104
35
3
2013 Number of VRCs: 1
C V A R I A N T R E V I E W C O M M I T T E E ( V R C )
R E T U R N O F R E S U L T S L I K E L Y P A T H
86
70
0
F I L T E R I N G / A N A L Y S I S / I N T E R P R E T A T I O N
V U S
Genomes Exomes
105
D N A S E Q U E N C I N G
N R
A
175
Number of Families
E N R O L L M E N T
CSER Study Overview
B
Number of Families
Whole genome and exome sequencing are being performed at an ever-‐ increasing rate. Due to the increased rate of sequencing and the rapid accumula;on of gene;c informa;on from both healthy and affected popula;ons, assessments of the pathogenicity of gene;c variants are extremely dynamic in nature. As a part of the CSER consor;um, we are performing sequencing on children with developmental delay/intellectual disability (DD/ID) and their parents. We have enrolled 296 families to date and have sequenced exomes from 368 individuals in 120 families and whole genomes from 389 individuals in 139 families. Within the group of 259 families for which analysis has currently been completed, ~58% of children enrolled in our study do not receive any findings related to their disease. Due to the rate of increase in available, published informa;on regarding genomic variants in the scien;fic community, and recognizing that some of our exome data was analyzed more than two years ago, we have systema;cally reanalyzed sequence data from pa;ents who did not receive informa;on about a poten;ally disease causal variant or those who received a variant of unknown significance.
35
2015 10
2016 2
75 60
59
45 30
29
15
21
11
0
P A T H
2014 10
31
>24
18-‐23 12-‐17 Time since original VRC (months)
1HudsonAlpha Ins;tute for Biotechnology, 2University of Alabama at Birmingham, 3University of Louisville
Background
Reanalysis Study Design A
140
A L I G N M E N T / G E N O T Y P I N G / A N N O T A T I O N
Unaffected!
104
35
3
2013 Number of VRCs: 1
C V A R I A N T R E V I E W C O M M I T T E E ( V R C )
R E T U R N O F R E S U L T S L I K E L Y P A T H
86
70
0
F I L T E R I N G / A N A L Y S I S / I N T E R P R E T A T I O N
V U S
Genomes Exomes
105
D N A S E Q U E N C I N G
N R
A
175
Number of Families
E N R O L L M E N T
CSER Study Overview
B
Number of Families
Whole genome and exome sequencing are being performed at an ever-‐ increasing rate. Due to the increased rate of sequencing and the rapid accumula;on of gene;c informa;on from both healthy and affected popula;ons, assessments of the pathogenicity of gene;c variants are extremely dynamic in nature. As a part of the CSER consor;um, we are performing sequencing on children with developmental delay/intellectual disability (DD/ID) and their parents. We have enrolled 296 families to date and have sequenced exomes from 368 individuals in 120 families and whole genomes from 389 individuals in 139 families. Within the group of 259 families for which analysis has currently been completed, ~58% of children enrolled in our study do not receive any findings related to their disease. Due to the rate of increase in available, published informa;on regarding genomic variants in the scien;fic community, and recognizing that some of our exome data was analyzed more than two years ago, we have systema;cally reanalyzed sequence data from pa;ents who did not receive informa;on about a poten;ally disease causal variant or those who received a variant of unknown significance.
35
2015 10
2016 2
75 60
59
45 30
29
15
21
11
0
P A T H
2014 10
31
>24
18-‐23 12-‐17 Time since original VRC (months)
