Classification rationale
Unclassified
No rationale recorded.
Final classification
Unclassified
PALB2
c.3549C>A
p.Tyr1183Ter
· exon NC_000016.10
LYFE Sciences is an AI system, and it can make mistakes. Criteria
may be applied incorrectly, sources may be misread, and a confident-looking
classification can still be wrong. Double-check every criterion and
its underlying evidence before relying on any call.
Gene diagram
· NM_024675.3 · variants mapped to exon structure
PALB2
NM_024675.3
Fetching transcript structure from UCSC…
Applied criteria · 0 applied · 28 assessed
MetEvidence satisfies this criterion.
Not metEvaluated against available evidence; threshold not reached.
Not assessedApplies in principle, but no evidence was found to evaluate it.
N/ADoesn't apply to this variant type.
Applied · 0
No criteria were applied for this variant.
Assessed · not applied
· 0 not met · 28 not assessed
Pathogenic
PVS1
PS1
PS2
PS3
PS4
PM1
PM2
PM3
PM4
PM5
PM6
PP1
PP2
PP3
PP4
PP5
Benign
BA1
BS1
BS2
BS3
BS4
BP1
BP2
BP3
BP4
BP5
BP6
BP7
Research & evidence
Population frequency
gnomAD v4.1
gnomAD v2.1
v4.1
This variant is present in gnomAD v4.1 (AF= 3.10151e-06; MAF= 0.00031%, 5/1612120 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 4.24356e-06; MAF= 0.00042%, 5/1178256 alleles, homozygotes = 0); grpmax FAF= 1.24e-06.
v2.1
This variant is present in gnomAD v2.1 (AF= 3.97741e-06; MAF= 0.00040%, 1/251420 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 8.79306e-06; MAF= 0.00088%, 1/113726 alleles, homozygotes = 0).
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
0.00031%
· 5 / 1,612,120
0 hom · FAF 0.00012%
0 hom · FAF 0.00012%
European (non-Finnish) 5 / 1,178,256 |
0.00042% |
+ 9 not observed (Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American)
gnomAD v2.1
0.0004%
· 1 / 251,420
0 hom
0 hom
European (non-Finnish) 1 / 113,726 |
0.00088% |
+ 7 not observed (African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian)
ClinVar
This variant has been reported in ClinVar as Pathogenic (22 clinical laboratories) and as pathogenic (1 clinical laboratory) and as Pathogenic by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 128144)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
Likely Oncogenic
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
COSMIC
Cancer hotspots
Somatic evidence
Not in COSMIC / hotspots
COSMIC
This variant has previously been reported in somatic cancers (COSMIC; COSV104552896, n = 1 times).
Hotspots
This variant does not lie in a statistically significant hotspot.
Sources & reference links
Triaged references · 9 PMIDs not cited in assessment
18053174 ↗
Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French-Canadian women.
ONCOKB
28279176 ↗
PALB2 mutations in BRCA1/2-mutation negative breast and ovarian cancer patients from Poland.
ONCOKB
28779002 ↗
Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.
ONCOKB
29484706 ↗
Identification of a novel truncating mutation in PALB2 gene by a multigene sequencing panel for mutational screening of breast cancer risk-associated and related genes.
ONCOKB
17200671 ↗
Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer.
CLINVAR
28492532 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.
CLINVAR