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.212-33A>C

CA269519

126634 (ClinVar)

Gene: PALB2

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6c7f2dd8-478c-4c7a-8a3c-4278300dc575

Approved on: 2023-06-15

Published on: 2023-06-15

HGVS expressions

NM_024675.4:c.212-33A>C

NM_024675.4(PALB2):c.212-33A>C

NC_000016.10:g.23636367T>G

CM000678.2:g.23636367T>G

NC_000016.9:g.23647688T>G

CM000678.1:g.23647688T>G

NC_000016.8:g.23555189T>G

NG_007406.1:g.9991A>C

ENST00000261584.9:c.212-33A>C

ENST00000261584.8:c.212-33A>C

ENST00000561514.1:c.218-33A>C

ENST00000565038.1:n.86+1483A>C

ENST00000567003.1:n.490-33A>C

ENST00000568219.5:c.-674-33A>C

NM_024675.3:c.212-33A>C

Likely Benign

BP7 BP4

PM2

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.212-33A>C variant in PALB2 is an intronic variant. BP7 applies because the threshold for the application of BP7 to deep intronic acceptor site variants is beyond position -21. The computational splicing predictor SpliceAI gives a score of 0.0 for acceptor loss suggesting that the variant has no impact on splicing. The highest population minor allele frequency in gnomAD v2.1.1 is 0.00006485 in the non-Finnish European population. (PM2_Supporting, BS1, and BA1 are not met). In summary, this variant meets the 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. (BP4, BP7)

BP7

The c.212-33A>C variant (NM_024675.3) is an intronic variant. BP7 applies because the threshold for the application of BP7 to deep intronic acceptor site variants is beyond position -21.

BP4

The computational splicing predictor SpliceAI gives a score of 0.0 for acceptor loss suggesting that the variant has no impact on splicing (BP4).

PM2

The highest population minor allele frequency in gnomAD v2.1.1 is 0.00006485 (1/15420 genomes) in the non-Finnish European population. (PM2_Supporting, BS1, and BA1 are not met)

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