Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
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Variant: NM_024675.3(PALB2):c.338C>T (p.Pro113Leu)

CA395137757

492220 (ClinVar)

Gene: PALB2
Condition: hereditary breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 663e53ff-bb0e-4265-9d15-68b52737ad99

HGVS expressions

NM_024675.3:c.338C>T
NM_024675.3(PALB2):c.338C>T (p.Pro113Leu)
NC_000016.10:g.23636208G>A
CM000678.2:g.23636208G>A
NC_000016.9:g.23647529G>A
CM000678.1:g.23647529G>A
NC_000016.8:g.23555030G>A
NG_007406.1:g.10150C>T
ENST00000261584.9:c.338C>T
ENST00000261584.8:c.338C>T
ENST00000565038.1:n.86+1642C>T
ENST00000567003.1:n.616C>T
ENST00000568219.5:c.-548C>T
NM_024675.4:c.338C>T
NM_024675.4(PALB2):c.338C>T (p.Pro113Leu)

Uncertain Significance

Met criteria codes 2
PM2_Supporting BP1
Not Met criteria codes 4
PP3 BA1 BS1 BP4

Evidence Links 0

Expert Panel

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.338C>T (p.Pro113Leu) variant in PALB2 is a missense variant predicted to cause substitution of proline by leucine at amino acid 113 (p.Pro113Leu). This variant is absent from gnomAD v2.1.1. PALB2, in which the variant was identified, is defined by the HBOP VCEP as a gene for which primarily truncating variants are known to cause disease. In summary, this variant meets the criteria to be classified as a 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. (PM2_Supporting, BP1)
Met criteria codes
PM2_Supporting
This variant is absent from gnomAD v2.1.1 and v3.1.1 (PM2_Supporting).
BP1
PALB2, in which the variant was identified, is defined by the ClinGen HBOP VCEP as a gene for which primarily truncating variants are known to cause disease (BP1).
Not Met criteria codes
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
The computational splicing predictor SpliceAI gives scores of AL: 0.00/DL: 0.00/AG: 0.00/DG: 0.00, suggesting that the variant has no impact on splicing. However, BP4 was not met since this variant has a putative protein effect.
Approved on: 2023-04-05
Published on: 2023-04-07
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