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]

Link to SEPIO compliant JSON-LD document

Variant: NM_024675.4:c.2787_2788dup

CA915941070

Gene: PALB2

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 5e667e74-d7fc-4604-bac1-2edcf9f0c2df

Approved on: 2023-04-05

Published on: 2023-04-07

HGVS expressions

NM_024675.4:c.2787_2788dup

NC_000016.10:g.23624057_23624058dup

CM000678.2:g.23624057_23624058dup

NC_000016.9:g.23635378_23635379dup

CM000678.1:g.23635378_23635379dup

NC_000016.8:g.23542879_23542880dup

NG_007406.1:g.22302_22303dup

ENST00000261584.9:c.2787_2788dup

ENST00000261584.8:c.2787_2788dup

ENST00000568219.5:c.1902_1903dup

NM_024675.3:c.2787_2788dup

Pathogenic

PM5_Supporting PM2_Supporting PVS1

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.2787_2788dup (p.Asn930Ilefs*6) variant in PALB2 is a frameshift variant predicted to cause a premature stop codon in biologically-relevant exon 8 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism. This variant is absent in gnomAD v2.1.1. 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. 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, PM2_Supporting, PM5_Supporting)

PM5_Supporting

This alteration results in a termination codon upstream of the most C-terminus pathogenic alteration (PALB2, p.Tyr1183*) as classified by the ClinGen HBOP Variant Curation Expert Panel, and is expected to be more deleterious (PM5_Supporting).

PM2_Supporting

Variant is absent in the GnomAD v2.1.1 (PM2_Supporting)

PVS1

The p.N930Ifs*6 variant is predicted to result in a premature stop codon that leads to truncated or absent protein (PVS1)

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