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_024675.3(PALB2):c.1794G>A (p.Leu598=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA350171

219588 (ClinVar)

Gene: PALB2

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 7ff87e24-773d-4049-8ff3-5d02e826b809

Approved on: 2023-04-05

Published on: 2023-04-07

HGVS expressions

NM_024675.3:c.1794G>A

NM_024675.3(PALB2):c.1794G>A (p.Leu598=)

NC_000016.10:g.23630360C>T

CM000678.2:g.23630360C>T

NC_000016.9:g.23641681C>T

CM000678.1:g.23641681C>T

NC_000016.8:g.23549182C>T

NG_007406.1:g.15998G>A

ENST00000261584.9:c.1794G>A

ENST00000261584.8:c.1794G>A

ENST00000565038.1:n.87-1085G>A

ENST00000568219.5:c.909G>A

NM_024675.4:c.1794G>A

NM_024675.4(PALB2):c.1794G>A (p.Leu598=)

Likely Benign

BP4 BP7 BS1

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.1794G>A (p.Leu598=) variant in PALB2 is a synonymous (silent) variant that is not predicted by MaxEntScan or SpliceAI to impact splicing. The highest population filtering allele frequency in gnomAD v2.1.1 is 0.0005689 in the African population, which is higher than the HBOP VCEP threshold (>0.0001) for BS1, and therefore meets this criterion. In summary, this variant meets criteria to be classified as likely benign 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 (BS1, BP4, BP7).

BP4

In silico predictors (MaxEntScan/SpliceAI) are in agreement that this variant is benign (BP4)

BP7

This is a synonymous (silent) variant (BP7)

BS1

GnomAD FAF 0.05689% (AFR) exceeds the PALB2 BS1 threshold of 0.01% (BS1)

Curation History

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