Gene Mutation Test Report

Molecule Tutorials - Herong's Tutorial Examples

∟Gene Mutation Test Report

Provides a tutorial example on how to read NGS (Next-Generation Sequencing) test reports Explanation of various terminologies are provided.

Understanding mutation naming convention can help us reading gene mutation test reports.

"1385-Gene Pan-Cancer Mutation Test" Report Example 1 - Part I

Report Date: 08 Sep 2017
ICD-10-CM: Acute myeloblastic leukemia, not having achieved remission
Tumor Tissue: Blood
Germline Tissue: Saliva

Gene:                     ERBB2
Aberration:               p.Ser310Phe
Tumor Allele Frequency:   23.34%
Coordinate Transcript ID: chr17:37868208 NM_004448    
NP_Number:                NP_004439.2
Variant Qualifier:        Test

Notes to help reading the above report:

"NGS" - Stands for Next Generation Sequencing technology
"ICD-10-CM" - Stands for International Classification of Diseases, Tenth Revision, Clinical Modification, coding standard.
"Tumor Tissue: Blood" - For somatic testing to identify mutations in the tumor
"Germline Tissue: Saliva" - For germline testing to identify mutations inherited from parents.
"Aberration" - Same as "Mutation".
"p.Ser310Phe" - Mutation description: "Ser" amino acid is replaced by "Phe" at position 310 in the protein.
"Tumor Allele Frequency" - The VAF (Variant Allele Frequency), also called MAF (Mutation Allele Frequency). But it is not the same as MAF (Minor Allele Frequency)! Tumor (tumor) is the variant in this case.
"Coordinate Transcript ID" - The location of the mutated gene.
"chr17:37868208 NM_004448" - The mutated gene is located at 37868208 in chromosome pair 17. The mutated gene accession number is "NM_004448".
"NP_Number" - The accession number of the protein expressed by the mutated gene.
"Variant Qualifier" - Not sure

"1385-Gene Pan-Cancer Mutation Test" Report Example 1 - Part II

UNCHARACTERIZED VARIANTS Test
                                                            Tumor Tumor
HGNC  Amino Acid   Loca                   Aberration        Read  Allele   
Gene  Change       -tion  Coordinate      Type              Depth Freq.
----- ------------ ------ --------------- ----------------- ----- ------
SPEN  p.Val1836Met exonic chr1:16258241   Nonsynonymous SNV  1398 48.64%
ATM   p.Val2439Ala exonic chr11:108200949 Nonsynonymous SNV   678 46.17%
PRSS8 p.Arg25Trp   exonic chr16:31146739                MNV   259 36.68%
PRSS8 p.Arg25Trp   exonic chr16:31146747  Nonsynonymous SNV   315 40.32%
ERBB2 p.Asp277Gly  exonic chr17:37866663  Nonsynonymous SNV   654 27.52%
PBRM1 p.Thr1380Asn exonic chr3:52597345   Nonsynonymous SNV   631 44.53%
ROS1  p.Gly1027Asp exonic chr6:117686261  Nonsynonymous SNV  1042 48.27%

Notes to help reading the above report:

"SNV" - Stands for Single-Nucleotide Variants
"MNV" - Stands for Multi-Nucleotide Variants
"Tumor Read Depth" - Number of reads that carry this tumor at the given Coordinate (address) of the chromosome sequence.

Note that we can not validate Tumor Allele Frequency values in the report, because total depths (total reads at given coordinates).

"1385-Gene Pan-Cancer Mutation Test" Report Example 2

Report Date: 2019-05-13
ICD10: D75.81 Myelofibrosis
Tumor Tissue: Bone Marrow
Germline Tissue: Saliva

Biomarkers   Variant Tiers
CALR         Tier 1
IDH1         Tier 1
DDX6         Tier 3
chr20q

Tier 1 - Variants of Strong Clinical Significance
  Gene   Variant       Pos              ENST                VAF      Depth
  CALR   p.Lys385fs    chr19:12943813   ENST00000316448.9   34.67%   1814
  IDH1   p.Arg132Ser   chr2:208248389   ENST00000345146.6   38.63%   2154

Tier 2 - Variants of possible Clinical Significance
  No variant.

Tier 3 - Variants of unknown Clinical Significance
  Gene   Variant       Pos               ENST                VAF      Depth
  DDX6   p.Ile179Thr   chr11:118765346   ENST00000526070.2   38.47%   2290