CPT 0161U: mRNA Sequence Analysis of PMS2 (CustomNext + RNA)

CPT code 0161U denotes a Proprietary Laboratory Analyses (PLA) code assigned to the CustomNext® + RNA: PMS2 test from Ambry Genetics®, used for mRNA sequence analysis of the PMS2 gene alongside the primary full sequence analysis code. PLA codes identify unique, manufacturer- or laboratory-specific tests and are important for tracking utilization, pricing, and clinical adoption of novel molecular assays. Nationally, PLA codes like 0161U matter because they signal specialized genetic diagnostics that can affect coverage policies, prior authorization practices, and laboratory reporting.

Key payers covered in this analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of the code’s clinical purpose and laboratory setting, summaries of payer coverage considerations, and the typical administrative elements associated with reporting a PLA molecular test. The publication outlines benchmark topics such as common modifier usage and claims processing considerations, summarizes policy and coding context relevant to proprietary molecular testing, and situates the code within the landscape of genetic diagnostics. Data not available in the input will be identified explicitly in relevant sections.

Billing Code Overview

CPT code 0161U is a Proprietary Laboratory Analyses (PLA) code reported for the CustomNext® + RNA: PMS2 test from Ambry Genetics®. The code applies to the mRNA sequence analysis of the PMS2 gene performed in conjunction with the primary code for full sequence analysis. This service is a molecular diagnostic laboratory test used to assess PMS2 gene mRNA sequences.

Service Type: Laboratory — Proprietary molecular diagnostic (PLA) testing

Typical Site of Service: Independent clinical reference laboratory or hospital molecular diagnostics laboratory

Clinical Context

A 42-year-old patient with a personal or strong family history of colorectal cancer and/or multiple adenomatous polyps is referred for hereditary cancer evaluation. Prior germline DNA sequencing identified a variant of uncertain significance or a complex genomic region in the PMS2 gene that limits standard DNA-based analysis. The ordering clinician (e.g., a geneticist or gastroenterologist) requests the CustomNext® + RNA: PMS2 test to perform mRNA sequence analysis of the PMS2 gene to clarify splice-altering variants or confirm the impact of DNA-level changes on transcript structure.

Specimen collection typically involves a peripheral blood draw collected in appropriate RNA-stabilizing tubes and shipped to Ambry Genetics® under the laboratory's instructions. The laboratory performs RNA extraction, reverse transcription, and targeted sequencing of PMS2 transcripts. Results reporting includes interpretation of whether observed splice variants affect the PMS2 transcript in a manner consistent with pathogenicity, and is reported in conjunction with the primary CPT for full sequence analysis. Typical sites of service include outpatient genetics clinics, gastroenterology or oncology clinics, and independent phlebotomy or ambulatory laboratory centers.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	When reporting the professional (interpretive) portion of a separate technical/professional split laboratory service if applicable.

Taxonomy Code	Specialty	Notes
2080P0200X	Clinical Genetics	Physicians specializing in medical genetics who order and interpret hereditary cancer testing.
207RC0000X	Gastroenterology	Gastroenterologists managing patients with hereditary colorectal cancer risk and ordering targeted PMS2 testing.
207Q00000X	Oncology	Medical oncologists involved in hereditary cancer assessment and treatment planning.
363L00000X	Clinical Laboratory	Laboratory directors and molecular diagnosticists performing or overseeing the RNA sequencing assay.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`Z15.09`	Genetic susceptibility to other malignant neoplasm	Indicates a personal or family history of genetic susceptibility where PMS2 RNA analysis may be ordered.
`Z80.0`	Family history of malignant neoplasm of digestive organs	Relevant when a family history of colorectal cancer prompts hereditary testing including PMS2 analysis.
`C18.9`	Malignant neoplasm of colon, unspecified	A colorectal cancer diagnosis where germline PMS2 evaluation may influence management.
`D12.6`	Benign neoplasm of colon	Presence of multiple polyps may prompt hereditary evaluation including PMS2 testing.
`Z85.038`	Personal history of other malignant neoplasm of large intestine	For surveillance and genetic evaluation following prior colorectal cancer.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`0161U`	CustomNext® + RNA: PMS2, mRNA sequence analysis of PMS2 gene (Proprietary Laboratory Analyses code)	Primary PLA code describing this specific RNA-based PMS2 transcript analysis; billed in conjunction with the primary full sequence analysis code for PMS2.
`81432`	Pathogenic variants analysis for germline genes by sequencing (multi-gene panel)	Commonly billed as the primary full sequence analysis for hereditary cancer panels; the RNA test supplements sequencing to clarify splice variants.
`88271`	Molecular cytogenetics; microarray (genomic) (e.g., array CGH)	Sometimes used in broader genetic evaluations for copy-number assessment when sequencing and RNA analysis indicate larger rearrangements.
`84999`	Unlisted chemistry procedure	Occasionally used historically for unique molecular tests when a specific PLA code was not available; now replaced by the PLA code for this proprietary test.
`99000`	Handling and/or conveyance of specimen for transfer from the office to a laboratory	Billed when specimen transport services are separately billable in accordance with payer rules.

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Summary & Overview