About PALB2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PALB2 c.3549C>A, p.(Tyr1183Ter)
Classification
Not classified
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. Select a step to read what it means.
Not classified yet.Select a step to read what it means.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
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.
01The reasoning
How it was classified
The recorded framework is ClinGen PALB2 VCEP v1.2.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 0
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Not classified
No source classification-combination explanation was recorded.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
5 / 1,612,120 alleles
gnomAD v4.1: 5 / 1,612,120 alleles. Recorded AF 3.10151e-06. Recorded homozygote count 0.
gnomAD 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).
No listed criterion applied
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
23 reported laboratory submissions
22 Pathogenic · 1 pathogenic.
Context only
ClinVar ↗
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV104552896, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen PALB2 VCEP v1.2.0, with the data and sources behind each one.
28 criteria with recorded statuses: 0 met · 0 not met · 28 not assessed · 0 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
No criteria match.
Not assessed · 28 · no assessment recorded
PVS1 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PS1 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PS2 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PS3 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PS4 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PM1 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PM2 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PM3 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PM4 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PM5 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PM6 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PP1 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PP2 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PP3 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PP4 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
PP5 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
BA1 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
BS1 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
BS2 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
BS3 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
BS4 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
BP1 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
BP2 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
BP3 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
BP4 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
BP5 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
BP6 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
BP7 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- PALB2
- Transcript
- NM_024675.3
- Coding (HGVS c.)
- NM_024675.3:c.3549C>A
- Protein (HGVS p.)
- NP_078951.2:p.(Tyr1183Ter)
- GRCh38
- chr16:23603471 G>T
- GRCh37
- chr16:23614792 G>T
- ClinVar
- 128144, 950529, 402305
- COSMIC
- COSV104552896
Gene diagram
Every interpreted variant in PALB2, mapped onto the exon structure of NM_024675.3. Select a row to find it on the plot.
PALB2NM_024675.3
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in PALB2
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
5 / 1,612,120 alleles
AF 3.1e-06 · 0 homozygotes · FAF 1.24e-06
gnomAD v2.1
1 / 251,420 alleles
AF 3.98e-06 · 0 homozygotes
By genetic ancestry
gnomAD v4.1
AF 3.1e-06 · 5 / 1,612,120 alleles · 0 hom · FAF 1.2e-06
| European (non-Finnish)5 / 1,178,256 | 4.2e-06 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 4e-06 · 1 / 251,420 alleles · 0 hom
| European (non-Finnish)1 / 113,726 | 8.8e-06 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals, South Asian.
Statements
gnomAD 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.
gnomAD 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).
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- 0.280
How the predictions were used
PP3 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
BP4 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
BP7 No criterion-specific rationale recorded. Details ▾Hide ▴
No further detail was recorded.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
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PMID 18053174 ↗Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French-Canadian women.No paper-specific finding is recorded.
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PMID 25529982 ↗A novel PALB2 truncating mutation in an Italian family with male breast cancer.No paper-specific finding is recorded.
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PMID 28279176 ↗PALB2 mutations in BRCA1/2-mutation negative breast and ovarian cancer patients from Poland.No paper-specific finding is recorded.
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PMID 28779002 ↗Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.No paper-specific finding is recorded.
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PMID 28858227 ↗The Role of PALB2 in the DNA Damage Response and Cancer Predisposition.No paper-specific finding is recorded.
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PMID 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.No paper-specific finding is recorded.
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PMID 17200671 ↗Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer.Reid S et al. · 2007No paper-specific finding is recorded.
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PMID 19264984 ↗Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene.Jones S et al. · 2009No paper-specific finding is recorded.
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
5 / 1,612,120 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
22 Pathogenic · 1 pathogenic
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1526222356
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/128144/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/16-23614792-G-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr16-23603471-G-T?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_024675.3%3Ac.3549…
- OncoKB ↗www.oncokb.org/gene/PALB2/Y1183*
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=107882943
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD 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.
gnomAD 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).
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)
Somatic
This variant has previously been reported in somatic cancers (COSMIC; COSV104552896, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.