Whole Exome Sequencing Uncovers Germline Variants of Cancer-Related Genes in Sporadic Pheochromocytoma

Table 2

Somatic and germline alterations identified in our cohort that could support PCC pathogenesis. Annotations concerning Exac frequency, COSMIC, ClinVar, and biological effect predictions are shown for each variant.

Sample

Gene

Somatic/germline

Position

Exon

cDna

Protein

Type

dbSNP

ExAC freq

COSMIC

ClinVar

Effect prediction

N47

SAMD9L

Germline

chr7:93133665

5

c.2307delC

p.N769fs

Frameshift

Novel

—

Yes

—

Pathogenic

N50

SAMD9L

Germline

chr7:93134756

6

c.1216C>T

p.R406X

Stop gain

rs150070697

0.002

Yes

—

Pathogenic

N54

SAMD9L

Somatic

chr7:93132925

4

c.3047T>C

p.L1016S

Missense

Novel

na

—

—

Pathogenic

N63

MAX

Germline SNV + somatic loss

chr14:65076665

7

c.397-2A>G

na

Splicing

Novel

—

Yes

—

Pathogenic

N51

VHL

Somatic + loss

chr3:10142040

1

c.193T>G

p.S65A

Missense

Novel

—

Yes

—

Pathogenic

N56

VHL

Somatic + loss

chr3:10142139

1

c.292T>C

p.Y98H

Missense

rs5030809

—

Yes

Pathogenic

Pathogenic

N55

NF1

Somatic + loss

chr17:31227548

20

c.2351delG

p.W784fs

Frameshift

Novel

—

Yes

—

Pathogenic

N62

NF1

Somatic + loss

chr17:31169890

5

c.480-1G>C

na

Splicing

Novel

—

Yes

—

Pathogenic

N53

RET

Somatic

chr10:43121968

16

c.2753T>C

p.M918T

Missense

rs74799832

—

Yes

Pathogenic

Pathogenic

N57

RET

Somatic

chr10:43114499

11

c.1899_1900insTGCCGC

p.L633delinsLCR

Nonframeshift insertion

Novel

—

Yes

—

Pathogenic

COSMIC record that totally match with the mutation identified; defined pathogenic if the mutation has been classified as pathogenic or deleterious by at least two out three predictors used (SIFT, Polyphen2, and LRT).