Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_024675.4(PALB2):c.839del (p.Asn280fs)

CA494462159

480243 (ClinVar)

Gene: PALB2 (HGNC:79728)

Condition: PALB2-related cancer predisposition (MONDO:0700272)

Inheritance Mode: Autosomal dominant inheritance

UUID: 00a3410e-0fb0-4098-8488-6a237f88c850

Approved on: 2023-04-05

Published on: 2025-09-16

HGVS expressions

NM_024675.4(PALB2):c.839del (p.Asn280fs)

NM_024675.4:c.839del

NC_000016.10:g.23635712del

CM000678.2:g.23635712del

NC_000016.9:g.23647033del

CM000678.1:g.23647033del

NC_000016.8:g.23554534del

NG_007406.1:g.10651del

ENST00000561514.3:c.845del

ENST00000565038.2:c.211+2143del

ENST00000566069.6:c.839del

ENST00000697377.2:c.845del

ENST00000697379.2:c.845del

ENST00000561514.2:c.-47del

ENST00000697374.1:c.-47del

ENST00000697375.1:n.2186del

ENST00000697376.1:c.-47del

ENST00000697377.1:c.-47del

ENST00000697378.1:n.1359del

ENST00000697379.1:c.-47del

ENST00000697382.1:c.-47del

ENST00000697383.1:c.48+5403del

ENST00000697384.1:n.993del

ENST00000261584.9:c.839del

ENST00000261584.8:c.839del

ENST00000565038.1:c.86+2143del

ENST00000568219.5:c.-47del

NM_024675.3:c.839del

Pathogenic

PVS1 PM2_Supporting PM5_Supporting

Evidence Links 0

Expert Panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

Criteria Specification Information

Criteria Specification: ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PALB2 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

The c.839del (p.Asn280fs) variant in PALB2 is a frameshift variant predicted to cause a premature stop codon in biologically-relevant exon 4 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism. This alteration results in a termination codon upstream of the most C-terminus pathogenic alteration (PALB2 p.Tyr1183*), as classified by the HBOP VCEP, and is expected to be more deleterious. This variant is absent from gnomAD v2.1.1. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant hereditary breast and pancreatic cancer and autosomal recessive FANCN based on the ACMG/AMP criteria applied, as specified by the HBOP VCEP (PVS1, PM5_Supporting, PM2_Supporting).

PVS1

The p.Asn280Thrfs*8 variant is predicted to result in a premature stop codon that leads to truncated or absent protein (PVS1)

PM2_Supporting

Variant is absent in the GnomAD cohort (PM2_Supporting)

PM5_Supporting

This alteration results in a termination codon upstream of the most C-terminus pathogenic alteration (PALB2 c.3549C>A (p.Tyr1183Ter)), as classified by the ClinGen Hereditary Breast, Ovarian, and Pancreatic Cancer VCEP, and is expected to be more deleterious (PM5_Supporting

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.