Mapping the genetic landscape of early-onset Alzheimer’s disease in a cohort of 36 families

Table 2 Pathogenic variants and rare VUS identified in dementia-related genes

Gene	Transcript	Nucleotide change	Amino acid change	MAF GnomAD Total	MAF GnomAD NFE	CADD (v1.3)
Pathogenic variants
APP^a	NM_000484	2149G>A	V717I	0	0	34
GRN	NM_002087	388_391delCAGT	Q130SfsX125	7.0^e−06	1.5^e−05	NA
PSEN1^b	NM_000021	786G>C	L262F	0	0	25.6
PSEN1	NM_000021	692C>T	A231V	0	0	34
PSEN1^a,b	NM_000021	236C>T	A79V	1.4^e−05	2.3^e−05	33
SORL1	NM_003105	2882_2885delCGCA	P961fs	0	0	NA
Variants of uncertain significance
ABCA7	NM_019112	3698G>A	R1233H	2.3^e−05	4.1^e−05	23.9
BIN1	NM_004305	746C>T	T249M	2.6^e−05	3.2^e−05	24.6
CR1	NM_000573	4162G>A	E1388K	0	0	24
FERMT2	NM_006832	667G>A	V223I	1.0^e−04	2.1^e−04	18.8
MADD	NM_003682	2308dupA	D769fs	2.0^e−04	4.3^e−04	NA
PRNP	NM_000311	130C>T	P44S	1.8^e−05	0	23.4
SORL1^c	NM_003105	4576G>T	A1526S	0	0	18.2
SQSTM1	NM_003900	c.420C>A	Y140X	0	0	35

^aPathological confirmation of AD in one affected patient carrying this variant. ^bDetected in two families. ^cConfirmed by Sanger sequencing and reported previously by Holstege et al., EJHG (2017). Abbreviations: MAF, minor allele frequency; NFE, non-Finnish European population

ISSN: 1758-9193