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.3543del (p.Phe1181fs)

CA1139664609

944799 (ClinVar)

Gene: PALB2

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: be5d98f5-78d2-43a2-9202-070e2afb4e4e

HGVS expressions

NM_024675.4:c.3543del

NM_024675.4(PALB2):c.3543del (p.Phe1181fs)

NC_000016.10:g.23603479del

CM000678.2:g.23603479del

NC_000016.9:g.23614800del

CM000678.1:g.23614800del

NC_000016.8:g.23522301del

NG_007406.1:g.42881del

ENST00000261584.9:c.3543del

ENST00000261584.8:c.3543del

ENST00000566069.5:n.309del

ENST00000568219.5:c.2658del

NM_024675.3:c.3543del

Uncertain Significance

PVS1_Strong PM2_Supporting

PM5

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.3543del (p.Phe1181fs) variant in PALB2 is a frameshift variant predicted to alter a region that is critical to protein function. The C-terminal end of the WD40 domain is substituted by an alternative extended sequence. This variant is absent from gnomAD v2.1.1. In summary, this variant meets criteria to be classified as variant of uncertain significance 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_Strong, PM2_Supporting)

PVS1_Strong

The c.3543del (p.Phe1181fs) variant in PALB2 is a frameshift variant predicted to alter a region that is critical to protein function in that the C-terminal end of the WD40 domain is substituted by an alternative extended sequence.

PM2_Supporting

Variant is absent in the GnomAD cohort (PM2_Supporting)

PM5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2023-06-01

Published on: 2023-06-15

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