About PALB2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PALB2 c.3044C>T, p.(Thr1015Ile)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
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: 1
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 1
BP1Supporting
BP1 · supporting
PALB2 VCEP BP1 applies to all missense variants in PALB2. The VCEP states: 'Based on published and unpublished functional studies, PALB2 has a low rate of missense variants that are non-functional in relevant assays. True missense pathogenic variants are not yet confirmed or refuted but are thought to be exceedingly rare.' NM_024675.4:c.3044C>T (p.Thr1015Ile) is a missense substitution and therefore BP1_Supporting is applied per VCEP rule.
Recorded classification: Uncertain significance
Richards et.al., 2015 - Combining rules v1.2.0 criteria-combination framework was evaluated deterministically with applied criteria: BP1 supporting benign; no rule matched the adjudicated criteria.
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
16 / 1,614,014 alleles
gnomAD v4.1: 16 / 1,614,014 alleles. Recorded AF 9.91317e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.1931e-05; MAF= 0.00119%, 3/251446 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.63764e-05; MAF= 0.00264%, 3/113738 alleles, homozygotes = 0); grpmax FAF= 7.01e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
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
7 reported laboratory submissions
6 Uncertain significance · 1 Likely benign.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PALB2, a scaffolding protein involved in DNA repair, is altered in various cancers.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
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.
27 criteria with recorded statuses: 1 met · 3 not met · 4 not assessed · 19 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_024675.4:c.3044C>T (p.Thr1015Ile) is a missense variant in PALB2, a gene in which loss-of-function is an established mechanism for autosomal dominant hereditary breast, ovarian, and pancreatic cancer predisposition.
This variant is present in gnomAD v4.1 at a total allele frequency of 0.00099% (16/1,614,014 alleles; grpmax FAF 0.000803%), predominantly in the European (non-Finnish) subpopulation. It is also present in gnomAD v2.1 at 0.00119% (3/251,446 alleles) and is absent from gnomAD-Canada.
This variant has been reported in ClinVar as Uncertain significance by 6 clinical laboratories and as Likely benign by 1 laboratory (ClinVar Variation ID 141554). No expert panel classifications are available.
In silico predictors yield mixed results: REVEL score 0.238 (below the 0.5 threshold commonly used for deleterious prediction), BayesDel score -0.308 (below the 0.0 threshold for benign prediction), and SpliceAI max delta 0.00 (no predicted splicing impact).
PALB2 VCEP BP1_Supporting is met: this criterion applies to all missense variants in PALB2 because true pathogenic missense variants are thought to be exceedingly rare, per the ClinGen HBOP VCEP v1.2.0.
PALB2 VCEP PM2_Supporting is not met: the variant frequency in gnomAD v4 (0.00099%) exceeds the VCEP threshold of ≤0.000333%. BS1 and BA1 are also not met as the grpmax FAF (0.000803%) does not exceed either the BS1 (>0.01%) or BA1 (>0.1%) thresholds.
Multiple PALB2 VCEP criteria are not applicable to missense variants by explicit VCEP rule: PVS1 (not a null variant), PS1, PM1, PM5, PP2, PP3, BP4, BP7. Additionally, PS2, PS3, PM6, PP4, PP5, BP2, BP3, BP5, BP6 are not applicable per VCEP framework.
PS4, PP1, BS2, and BS4 could not be assessed due to absence of variant-specific case-control, segregation, or Fanconi Anemia proband data in the evidence reviewed.
No reviewed publication (10 PMIDs screened, 5 full-text papers read) mentioned NM_024675.4:c.3044C>T. None of the ClinVar-submitted PMIDs contained variant-specific evidence for this missense.
With only BP1_Supporting (supporting benign) met and no pathogenic criteria met, this variant is classified as Uncertain Significance (VUS) per ACMG/AMP 2015 combining rules. The single supporting benign criterion is insufficient for Likely Benign classification, which requires ≥2 supporting benign criteria or 1 strong benign + 1 supporting benign.
No criteria match.
Met · 1
BP1 SupportingPALB2 VCEP BP1 applies to all missense variants in PALB2. The VCEP states: 'Based on published and unpublished functional studies, PALB2 has a low rate of missense variants that are non-functional in relevant assays. True missense pathogenic variants are not yet confirmed or refuted but are thought to be exceedingly rare.' NM_024675.4:c.3044C>T (p.Thr1015Ile) is a missense substitution and therefore BP1_Supporting is applied per VCEP rule. Details ▾Hide ▴
Evidence considered
- Missense variant in PALB2
- VCEP BP1 rule applies to all missense variants.
Sources
Not met · 3 · evaluated, threshold not reached
PM2 PALB2 VCEP PM2_Supporting requires frequency ≤0.000333% (1/300,000) in gnomAD v4. This variant has total AF = 9.91e-06 (0.00099%, 16/1,614,014 alleles) in gnomAD v4.1, which exceeds the threshold. The variant is present in 16 alleles, predominantly in the European (non-Finnish) subpopulation. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: AF=0.00099% (16/1
- 614
- 014)
- exceeds PM2 threshold of 0.000333%.
Sources
BA1 PALB2 VCEP BA1 requires grpmax filtering AF >0.1% in gnomAD v4. This variant has grpmax FAF = 8.03e-06 (0.000803%) in gnomAD v4.1, well below the stand-alone benign threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF=0.000803%
- below BA1 threshold of >0.1%.
Sources
BS1 PALB2 VCEP BS1 requires grpmax filtering AF >0.01% in gnomAD v4. This variant has grpmax FAF = 8.03e-06 (0.000803%) in gnomAD v4.1, below the strong benign threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF=0.000803%
- below BS1 threshold of >0.01%.
Sources
Not assessed · 4 · no assessment recorded
PS4 PALB2 VCEP PS4 requires case-control studies with p≤0.05 AND (OR≥3 OR lower 95% CI ≥1.5). No case-control data for NM_024675.4:c.3044C>T were identified in any reviewed publication. The BCAC study (PMID:33471991) analyzed breast cancer risk genes but did not report variant-specific odds ratios for this missense. Details ▾Hide ▴
Evidence considered
- No variant-specific case-control data available.
Still missing
- Absence of case-control data for this specific missense variant.
Sources
PP1 PALB2 VCEP PP1 requires quantitative co-segregation analysis (LOD scores or Bayes Factors for AD; affected relative counts for AR). No co-segregation data for NM_024675.4:c.3044C>T were identified in any reviewed publication. Details ▾Hide ▴
Evidence considered
- No segregation data available for this variant.
Still missing
- Absence of familial co-segregation data.
Sources
BS2 PALB2 VCEP BS2 requires Fanconi Anemia proband data scored via the BS2 point table. No Fanconi Anemia proband data are available for NM_024675.4:c.3044C>T in the evidence reviewed. The variant is absent from COSMIC and has no reported homozygous observations. Details ▾Hide ▴
Evidence considered
- No Fanconi Anemia proband data available
- variant absent from COSMIC.
Still missing
- Absence of Fanconi Anemia proband data for BS2 point scoring.
Sources
BS4 PALB2 VCEP BS4 requires quantitative co-segregation analysis (LOD scores or Bayes Factors). No segregation data for NM_024675.4:c.3044C>T were identified in any reviewed publication. Details ▾Hide ▴
Evidence considered
- No segregation/LOD data available for this variant.
Still missing
- Absence of co-segregation data for BS4 analysis.
Sources
Not applicable · 19· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_024675.4:c.3044C>T is a missense variant (p.Thr1015Ile), not a null variant (nonsense, frameshift, or canonical splice site). The PALB2 VCEP PVS1 decision tree applies to truncating and splice variants, not missense substitutions. Details ▾Hide ▴
Evidence considered
- Missense substitution at c.3044 (exon 10)
- variant bucket 'other'
- not a null variant.
Sources
pvs1_variant_assessmentcspec ↗
PS1 N/APALB2 VCEP explicitly states: 'Missense: Do not use. Missense changes are not yet confirmed as a mechanism of disease for PALB2.' The PS1 splicing table is intended for splice-altering variants only. Details ▾Hide ▴
PS2 VCEPPALB2 VCEP marks PS2 as not applicable for both autosomal dominant and autosomal recessive disease; informative de novo occurrences have not been observed for PALB2. Details ▾Hide ▴
PS3 VCEPPALB2 VCEP marks PS3 as not applicable; functional protein assays are not validated for PALB2 missense variant interpretation per VCEP guidance. Details ▾Hide ▴
PM1 VCEPPALB2 VCEP marks PM1 as not applicable: 'Missense pathogenic variation in PALB2 is not yet confirmed as a mechanism of disease.' Details ▾Hide ▴
PM5 N/APALB2 VCEP states: 'Do not use for missense changes: Missense changes are not yet confirmed as a mechanism of disease for PALB2.' PM5 in this VCEP applies only to frameshifting/truncating variants with premature termination codons upstream of p.Tyr1183, or splice variants with confirmed NMD-prone splicing impact. Details ▾Hide ▴
Evidence considered
- VCEP PM5 excludes missense variants
- PM5 mode is truncation-cutoff gene-specific
- not classic same-residue missense.
Sources
cspec ↗pm5_candidates
PM6 VCEPPALB2 VCEP marks PM6 as not applicable: 'Informative de novo occurrences have not yet been observed and de novo AR conditions are unlikely to be informed by phase.' Details ▾Hide ▴
PP2 VCEPPALB2 VCEP marks PP2 as not applicable: 'Missense is not yet confirmed or refuted as a mechanism of disease for PALB2.' Details ▾Hide ▴
PP3 N/APALB2 VCEP states: 'Missense: Do not use.' While SpliceAI max delta = 0.00 (no predicted splicing impact), REVEL = 0.238, and BayesDel = -0.308, the VCEP explicitly excludes missense variants from PP3 because published predictors have not achieved reliable functional outcome prediction for PALB2 missense variants. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta=0.00
- REVEL=0.238
- BayesDel=-0.308
- VCEP excludes missense from PP3.
Sources
PP4 VCEPPALB2 VCEP marks PP4 as not applicable: breast cancer has multiple genetic etiologies and no features readily distinguish hereditary from sporadic causes. Details ▾Hide ▴
PP5 VCEPPALB2 VCEP marks PP5 as 'Not Applicable for this VCEP' per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation. Details ▾Hide ▴
BS3 VCEPPALB2 VCEP marks BS3 as not applicable; functional protein assays are not validated for PALB2 variant interpretation per VCEP guidance. Details ▾Hide ▴
BP2 VCEPPALB2 VCEP marks BP2 as not applicable for this gene; use ATM PM3/BP2 table instead per VCEP guidance. Details ▾Hide ▴
BP3 VCEPSkipped per instructions. PALB2 VCEP also marks BP3 as not applicable: small in-frame losses are neither confirmed nor refuted as a mechanism of pathogenicity. Details ▾Hide ▴
No further detail was recorded.
BP4 N/APALB2 VCEP states: 'Missense: Do not use.' BP4 for splice predictions is not applicable to missense variants; SpliceAI max delta = 0.00, confirming no predicted splicing impact, but the VCEP rule excludes missense variants regardless. Details ▾Hide ▴
Evidence considered
- VCEP BP4 excludes missense variants
- SpliceAI max delta=0.00.
Sources
BP5 VCEPPALB2 VCEP marks BP5 as not applicable: cases with multiple pathogenic variants have been observed with no noticeable difference in phenotype, and PALB2 has moderate penetrance. Details ▾Hide ▴
BP6 VCEPPALB2 VCEP marks BP6 as 'Not Applicable for this VCEP' per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation. Details ▾Hide ▴
BP7 N/ABP7 applies to synonymous variants and deep intronic variants (beyond +7 donor / -21 acceptor). NM_024675.4:c.3044C>T is a missense variant (p.Thr1015Ile), not a synonymous or deep intronic substitution. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is for synonymous and deep intronic variants only.
Sources
PS5 N/APS5 is not defined as a criterion in the PALB2 VCEP framework (ClinGen HBOP VCEP v1.2.0). The criterion is absent from the VCEP criteria list. Details ▾Hide ▴
Identifiers
- Gene
- PALB2
- Transcript
- NM_024675.4
- Coding (HGVS c.)
- NM_024675.4:c.3044C>T
- Protein (HGVS p.)
- NP_078951.2:p.(Thr1015Ile)
- GRCh38
- chr16:23621431 G>A
- GRCh37
- chr16:23632752 G>A
- ClinVar
- 141554
Gene diagram
Every interpreted variant in PALB2, mapped onto the exon structure of NM_024675.4. Select a row to find it on the plot.
PALB2NM_024675.4
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
16 / 1,614,014 alleles
AF 9.91e-06 · 0 homozygotes · FAF 8.03e-06
gnomAD v2.1
3 / 251,446 alleles
AF 1.19e-05 · 0 homozygotes · FAF 7.01e-06
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 9.9e-06 · 16 / 1,614,014 alleles · 0 hom · FAF 8e-06
| European (non-Finnish)16 / 1,180,006 | 1.4e-05 |
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 1.2e-05 · 3 / 251,446 alleles · 0 hom · FAF 7e-06
| European (non-Finnish)3 / 113,738 | 2.6e-05 |
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= 9.91317e-06; MAF= 0.00099%, 16/1614014 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.35593e-05; MAF= 0.00136%, 16/1180006 alleles, homozygotes = 0); grpmax FAF= 8.03e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.1931e-05; MAF= 0.00119%, 3/251446 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.63764e-05; MAF= 0.00264%, 3/113738 alleles, homozygotes = 0); grpmax FAF= 7.01e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.238
- BayesDel
- -0.308
How the predictions were used
PP3 N/APALB2 VCEP states: 'Missense: Do not use.' While SpliceAI max delta = 0.00 (no predicted splicing impact), REVEL = 0.238, and BayesDel = -0.308, the VCEP explicitly excludes missense variants from PP3 because published predictors have not achieved reliable functional outcome prediction for PALB2 missense variants. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta=0.00
- REVEL=0.238
- BayesDel=-0.308
- VCEP excludes missense from PP3.
Sources
BP4 N/APALB2 VCEP states: 'Missense: Do not use.' BP4 for splice predictions is not applicable to missense variants; SpliceAI max delta = 0.00, confirming no predicted splicing impact, but the VCEP rule excludes missense variants regardless. Details ▾Hide ▴
Evidence considered
- VCEP BP4 excludes missense variants
- SpliceAI max delta=0.00.
Sources
BP7 N/ABP7 applies to synonymous variants and deep intronic variants (beyond +7 donor / -21 acceptor). NM_024675.4:c.3044C>T is a missense variant (p.Thr1015Ile), not a synonymous or deep intronic substitution. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is for synonymous and deep intronic variants only.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.238. BayesDel score = -0.308316.
8 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 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.ACMG/AMP standards and guidelines for the interpretation of sequence variants. This is a methodological framework document; NM_024675.4:c.3044C>T is not discussed.Does not name this variant
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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.Decker B et al. · 2017Case-control sequencing study of ATM, CHEK2, PALB2, and XRCC2 in 13,087 breast cancer cases and 5,488 controls. Truncating variants in PALB2 were associated with increased breast cancer risk (OR=4.69, 95% CI 2.27-9.68). The paper notes that rare missense variants in PALB2 may contribute to risk but larger studies are needed. NM_024675.4:c.3044C>T was not identified in this paper.Does not name this variant
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PMID 34242744 ↗Customizing local and systemic therapies for women with early breast cancer: the St. Gallen International Consensus Guidelines for treatment of early breast cancer 2021.The full-text file retrieved for PMID:34242744 does not correspond to the St. Gallen International Consensus Guidelines. The retrieved content is an unrelated Portuguese-language philosophy article. The variant could not be assessed from this source.Does not name this variant
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PMID 17508274 ↗Risk assessment and genetic counseling for hereditary breast and ovarian cancer: recommendations of the National Society of Genetic Counselors.Berliner JL et al. · 2007National Society of Genetic Counselors recommendations for risk assessment and genetic counseling for hereditary breast and ovarian cancer. This is a clinical practice guideline focused on BRCA1/BRCA2 counseling; NM_024675.4:c.3044C>T is not discussed.Does not name this variant
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PMID 24366402 ↗Summaries for patients. Assessing the genetic risk for BRCA-related breast or ovarian cancer in women: recommendations from the U.S. Preventive Services Task Force.2014Patient summary of USPSTF recommendations on BRCA-related cancer risk assessment. This is a lay-language summary with no variant-level data. NM_024675.4:c.3044C>T is not discussed.Does not name this variant
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PMID 25085752 ↗Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes.Pruss D et al. · 2014Development and validation of a statistical algorithm for reclassification of BRCA1 and BRCA2 variants of uncertain significance. The paper focuses exclusively on BRCA1 and BRCA2; PALB2 is not discussed. NM_024675.4:c.3044C>T was not identified.Does not name this variant
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PMID 31479213 ↗PMID 31479213No paper-specific finding is recorded.
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PMID 33471991 ↗Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.Breast Cancer Association Consortium et al. · 2021Breast Cancer Association Consortium study analyzing 34 putative susceptibility genes in 60,466 breast cancer cases and 53,461 controls. The abstract reports gene-level associations but does not list individual variants. NM_024675.4:c.3044C>T was not mentioned in the abstract.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
16 / 1,614,014 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
6 Uncertain significance · 1 Likely benign
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/141554/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/16-23632752-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr16-23621431-G-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/16-23621431-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_024675.4%3Ac.3044…
- OncoKB ↗www.oncokb.org/gene/PALB2/T1015I
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=PALB2+c.3044C%3ET
- 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= 9.91317e-06; MAF= 0.00099%, 16/1614014 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.35593e-05; MAF= 0.00136%, 16/1180006 alleles, homozygotes = 0); grpmax FAF= 8.03e-06.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.1931e-05; MAF= 0.00119%, 3/251446 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.63764e-05; MAF= 0.00264%, 3/113738 alleles, homozygotes = 0); grpmax FAF= 7.01e-06.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (6 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 141554)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.238. BayesDel score = -0.308316.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PALB2, a scaffolding protein involved in DNA repair, is altered in various cancers.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.