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(PALB2):c.7G>T (p.Glu3Ter)

CA10583388

241571 (ClinVar)

Gene: PALB2

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: fe8de8d5-9fd0-4d86-9572-d14485246aff

Approved on: 2023-04-05

Published on: 2023-04-07

HGVS expressions

NM_024675.4:c.7G>T

NM_024675.4(PALB2):c.7G>T (p.Glu3Ter)

NC_000016.10:g.23641151C>A

CM000678.2:g.23641151C>A

NC_000016.9:g.23652472C>A

CM000678.1:g.23652472C>A

NC_000016.8:g.23559973C>A

NG_007406.1:g.5207G>T

ENST00000261584.9:c.7G>T

ENST00000261584.8:c.7G>T

ENST00000567003.1:n.151G>T

ENST00000568219.5:c.-862G>T

NM_024675.3:c.7G>T

Pathogenic

PVS1 PM2_Supporting PM5_Supporting

BP7

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.7G>T (p.Glu3Ter) variant in PALB2 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 1 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 c.7G>T (p.Glu3Ter) variant in PALB2 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 1/13 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism.

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_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).

BP7

No impact on splicing by SpliceAI

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