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

CA269519

126634 (ClinVar)

Gene: PALB2

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

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

• Met criteria codes: BP4 BP7

• Not Met criteria codes: PM2

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

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)

Met criteria codes

• 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).
• 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.

Not Met criteria codes

• 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)