About PALB2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PALB2 c.1096A>G, p.(Asn366Asp)
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. 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: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
This variant is extremely rare in population databases, with a total allele frequency of 4.96e-06 (0.00000050%) in gnomAD v4.1, well below the PALB2 VCEP PM2_Supporting threshold of ≤ 0.000333% (1/300,000). All 8 observed alleles are in the South Asian subpopulation (AF = 0.00878%), but the VCEP exception is for n=1 with frequency > 0.0003% and does not apply here.
Benign criteria applied · 1
BP1Supporting
BP1 · supporting
The PALB2 VCEP explicitly applies BP1 at supporting level to all missense variants in PALB2. True missense pathogenic variants are thought to be exceedingly rare, and the gene has a low rate of missense variants that are non-functional in relevant assays. NM_024675.4:c.1096A>G (p.Asn366Asp) is a missense variant and therefore receives BP1.
Recorded classification: Not classified
ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PALB2 Version 1.2 v1.2 criteria-combination framework: matched Rule31 (Benign.Supporting >=1 + Pathogenic.Supporting >=1) with applied criteria: PM2 supporting, BP1 supporting benign; maps to Uncertain Significance - Conflicting Evidence.
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
8 / 1,614,152 alleles
gnomAD v4.1: 8 / 1,614,152 alleles. Recorded AF 4.95616e-06. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
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
6 reported laboratory submissions
5 Uncertain significance · 1 Likely benign. ClinVar API review status: criteria provided, conflicting classifications.
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, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 6 not met · 0 not assessed · 18 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.1096A>G (p.Asn366Asp) is a missense variant in PALB2 with an extremely low population frequency in gnomAD v4.1 (total AF = 4.96e-06, 8/1,614,152 alleles, 0 homozygotes), meeting PM2_Supporting under the PALB2 VCEP threshold of ≤ 0.000333%.
Under the PALB2 HBOP VCEP v1.2, BP1 is applied at supporting benign level to all PALB2 missense variants. Missense pathogenic variation in PALB2 is not yet confirmed as a mechanism of disease, and true missense pathogenic variants are thought to be exceedingly rare.
This variant has been reported in ClinVar as Uncertain significance by 5 clinical laboratories and Likely benign by 1 laboratory (VCV000188117), with an overall review status of 'criteria provided, single submitter.' No expert panel has reviewed this variant.
SpliceAI predicts no splicing impact (max delta = 0.00). In silico missense predictors (REVEL = 0.046, BayesDel = -0.707777) lean toward benign, but the PALB2 VCEP does not permit the use of PP3 or BP4 for missense variants.
The majority of ACMG criteria are not applicable under the PALB2 VCEP for missense variants: PVS1 (not a null variant), PS1/PS3/PM1/PP2 (missense pathogenic variation not confirmed), PS5 (not in VCEP), PM5 (truncation-only rule), PP3/BP4 (missense not used), PS2/PM6 (de novo not applicable), PP4/BP5 (not applicable per VCEP), BP7 (not synonymous), PP5/BP6 (not for use per VCEP).
With one pathogenic supporting criterion (PM2_Supporting) and one benign supporting criterion (BP1), the evidence is balanced and insufficient to classify this variant as pathogenic or benign. The variant is classified as Uncertain Significance under PALB2 VCEP v1.2 combination rules.
No criteria match.
Met · 2
PM2 SupportingThis variant is extremely rare in population databases, with a total allele frequency of 4.96e-06 (0.00000050%) in gnomAD v4.1, well below the PALB2 VCEP PM2_Supporting threshold of ≤ 0.000333% (1/300,000). All 8 observed alleles are in the South Asian subpopulation (AF = 0.00878%), but the VCEP exception is for n=1 with frequency > 0.0003% and does not apply here. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 total AF = 4.95616e-06 (8/1
- 614
- 152 alleles
- 0 homozygotes)
- grpmax FAF = 4.368e-05 (0.00004368%)
- VCEP PM2 threshold: frequency ≤ 0.000333% in gnomAD v4
Sources
BP1 SupportingThe PALB2 VCEP explicitly applies BP1 at supporting level to all missense variants in PALB2. True missense pathogenic variants are thought to be exceedingly rare, and the gene has a low rate of missense variants that are non-functional in relevant assays. NM_024675.4:c.1096A>G (p.Asn366Asp) is a missense variant and therefore receives BP1. Details ▾Hide ▴
Evidence considered
- VCEP BP1: 'Apply to all missense variants.'
- VCEP: '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.'
Sources
Not met · 6 · evaluated, threshold not reached
PS4 No case-control study data are available for NM_024675.4:c.1096A>G to demonstrate significantly increased prevalence in affected individuals versus controls. The PALB2 VCEP requires a case-control study with p ≤ 0.05 and OR/RR/HR ≥ 3 or lower 95% CI ≥ 1.5. Details ▾Hide ▴
Evidence considered
- No case-control data available for this variant in the evidence packet.
Still missing
- No published case-control or proband-counting studies identified for this variant.
Sources
PP1 No co-segregation data are available for this variant. Quantitative co-segregation analysis is mandated by the PALB2 VCEP for PP1 assessment, and no LOD scores or family segregation data exist in the evidence packet. Details ▾Hide ▴
Evidence considered
- No segregation data or LOD scores available for this variant.
Still missing
- No family segregation studies identified.
Sources
BA1 The PALB2 VCEP BA1 threshold is grpmax filtering allele frequency > 0.1% in gnomAD v4. The observed grpmax FAF is 4.368e-05 (0.00004368%), which is far below the 0.1% threshold. This variant is too rare to satisfy BA1. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 4.368e-05 (0.00004368%)
- VCEP BA1 threshold: grpmax FAF > 0.1%
Sources
BS1 The PALB2 VCEP BS1 threshold is grpmax filtering allele frequency > 0.01% in gnomAD v4. The observed grpmax FAF is 4.368e-05 (0.00004368%), which is well below the 0.01% threshold. This variant is too rare to satisfy BS1. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 4.368e-05 (0.00004368%)
- VCEP BS1 threshold: grpmax FAF > 0.01%
Sources
BS2 The PALB2 VCEP BS2 criterion requires proband-level data per the Fanconi Anemia BS2 tables. No homozygous or compound heterozygous proband data are available in the evidence packet. The 8 heterozygous observations in gnomAD v4 are from a population-based cohort and are explicitly excluded from BS2 per VCEP instructions. Details ▾Hide ▴
Evidence considered
- No Fanconi Anemia proband data available.
- VCEP: 'Do not use for individuals in population based cohorts
- such as gnomAD.'
Still missing
- No clinical proband data with homozygous or compound heterozygous status for Fanconi anemia.
Sources
BS4 No co-segregation data are available to demonstrate lack of segregation with disease. The PALB2 VCEP requires quantitative co-segregation analysis with LOD scores for BS4 application. Details ▾Hide ▴
Evidence considered
- No segregation data or LOD scores available.
Still missing
- No family segregation studies identified for BS4 evaluation.
Sources
Not applicable · 18· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 applies only to null variants (nonsense, frameshift, canonical splice sites). NM_024675.4:c.1096A>G is a missense variant (p.Asn366Asp) and does not qualify for PVS1 under the PALB2 VCEP PVS1 Decision Tree. Details ▾Hide ▴
Evidence considered
- Missense substitution does not fall into any null-variant bucket.
- PVS1 gene gate is eligible for PALB2 but the variant class is missense
- not a null variant.
Sources
cspec ↗pvs1_variant_assessment
PS1 N/AThe PALB2 VCEP specifies that PS1 is not to be used for missense variants because missense pathogenic variation in PALB2 is not yet confirmed as a mechanism of disease. The PS1 Splicing table is only applicable for variants with a predicted splicing effect, and SpliceAI max delta score is 0.00 (no splicing impact). Details ▾Hide ▴
Evidence considered
- VCEP PS1 instructions: 'Missense: Do not use.'
- SpliceAI max delta = 0.00
- no splicing impact predicted.
Sources
PS2 VCEPThe PALB2 VCEP marks PS2 as not applicable: informative de novo occurrences have not yet been observed for autosomal dominant PALB2-related cancer predisposition, and de novo is unlikely for this common cancer phenotype. Details ▾Hide ▴
PS3 VCEPThe PALB2 VCEP marks PS3 as not applicable for protein-level functional assays. No well-established functional studies have been validated and shown reproducible and robust performance in a clinical diagnostic laboratory setting for PALB2 missense variants. Details ▾Hide ▴
PM1 VCEPThe PALB2 VCEP explicitly states: 'Do not use. Missense pathogenic variation in PALB2 is not yet confirmed as a mechanism of disease.' PM1 is not to be applied for PALB2 missense variants. Details ▾Hide ▴
Evidence considered
- VCEP: PM1 applicability = Not applicable.
- VCEP instructions: 'Do not use: Missense pathogenic variation in PALB2 is not yet confirmed as a mechanism of disease.'
Sources
PM5 N/AThe PALB2 VCEP PM5 rule applies only to frameshifting or truncating variants with premature termination codons upstream of p.Tyr1183, or splice variants with NMD-prone premature termination. This missense variant (p.Asn366Asp) does not fit either category, and the VCEP explicitly states: 'Do not use for missense changes.' Details ▾Hide ▴
Evidence considered
- VCEP: PM5 applies only to truncating/frameshifting variants upstream of p.Tyr1183 and splice variants.
- VCEP: 'Do not use for missense changes.'
Sources
cspec ↗pm5_candidates
PM6 VCEPThe PALB2 VCEP marks PM6 as not applicable for both autosomal dominant and autosomal recessive disease: informative de novo occurrences have not been observed, and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
PP2 VCEPThe PALB2 VCEP explicitly states: 'Do not use. Missense is not yet confirmed or refuted as a mechanism of disease for PALB2.' PP2 is not to be applied for PALB2 missense variants. Details ▾Hide ▴
Evidence considered
- VCEP: PP2 applicability = Not applicable.
- VCEP: 'Do not use. Missense is not yet confirmed or refuted as a mechanism of disease for PALB2.'
Sources
PP3 N/AThe PALB2 VCEP PP3 rule states: 'Missense: Do not use.' The only applicable PP3 path is for splicing predictions (SpliceAI ≥ 0.2), and this variant has a SpliceAI max delta score of 0.00, indicating no predicted splicing impact. REVEL score is 0.046 and BayesDel score is -0.707777, both leaning toward benign, but in silico missense predictors are not to be used per VCEP. Details ▾Hide ▴
Evidence considered
- VCEP PP3: 'Missense: Do not use.'
- SpliceAI max delta = 0.00 (no splicing impact).
- REVEL = 0.046 (not used per VCEP).
- BayesDel = -0.707777 (not used per VCEP).
Sources
PP4 VCEPThe PALB2 VCEP marks PP4 as not applicable for autosomal dominant disease because breast cancer has multiple genetic etiologies (genetic heterogeneity) and there are no features that can readily distinguish hereditary from sporadic causes. Details ▾Hide ▴
PP5 VCEPThe PALB2 VCEP explicitly marks PP5 as 'Not Applicable for this VCEP' as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. This criterion is not for use in PALB2 variant interpretation. Details ▾Hide ▴
BS3 VCEPThe PALB2 VCEP marks BS3 as not applicable. Well-established functional studies showing no damaging effect on PALB2 protein function or splicing are not available for this missense variant. Details ▾Hide ▴
BP2 VCEPThe PALB2 VCEP marks BP2 as not applicable for this gene. Observed in trans/cis data for PALB2 should be evaluated through the ATM PM3/BP2 table which is not applicable here. Details ▾Hide ▴
BP4 N/AThe PALB2 VCEP BP4 rule explicitly states: 'Missense: Do not use.' The splicing component of BP4 (SpliceAI ≤ 0.1 with no predicted splicing impact) is not to be applied for missense variants per the VCEP. REVEL (0.046) and BayesDel (-0.707777) are not used because published predictors have not been validated for PALB2 missense functional outcome. Details ▾Hide ▴
Evidence considered
- VCEP BP4: 'Missense: Do not use.'
- SpliceAI max delta = 0.00 is consistent with no splicing impact but BP4 is not to be applied for missense.
- REVEL = 0.046
- BayesDel = -0.707777 (not used per VCEP).
Sources
BP5 VCEPThe PALB2 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, making co-occurrence with other pathogenic variants more common in the population. Details ▾Hide ▴
BP6 VCEPThe PALB2 VCEP explicitly marks BP6 as 'Not Applicable for this VCEP' as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP7 N/ABP7 applies to synonymous and deep intronic variants. NM_024675.4:c.1096A>G is a missense variant (p.Asn366Asp) and does not qualify for BP7 under standard ACMG/AMP guidelines or the PALB2 VCEP. Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is for synonymous and deep intronic variants only.
Sources
PS5 N/AThe PALB2 VCEP does not list PS5 as a standalone criterion. Missense pathogenic variation in PALB2 is not yet confirmed as a mechanism of disease, and the VCEP delegates same-codon comparisons to the PS1 Splicing table, which is not applicable to this missense variant. Details ▾Hide ▴
Evidence considered
- PS5 not defined in PALB2 VCEP criteria set
- VCEP states missense pathogenic variation is not confirmed.
Sources
Identifiers
- Gene
- PALB2
- Transcript
- NM_024675.4
- Coding (HGVS c.)
- NM_024675.4:c.1096A>G
- Protein (HGVS p.)
- NP_078951.2:p.(Asn366Asp)
- GRCh38
- chr16:23635450 T>C
- GRCh37
- chr16:23646771 T>C
- ClinVar
- 188117
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
8 / 1,614,152 alleles
AF 4.96e-06 · 0 homozygotes · FAF 4.37e-05
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 5e-06 · 8 / 1,614,152 alleles · 0 hom · FAF 4.4e-05
| South Asian8 / 91,088 | 8.8e-05 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, African/African American, European (non-Finnish).
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 4.95616e-06; MAF= 0.00050%, 8/1614152 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 8.78272e-05; MAF= 0.00878%, 8/91088 alleles, homozygotes = 0); grpmax FAF= 4.368e-05.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.046
- BayesDel
- -0.708
How the predictions were used
PP3 N/AThe PALB2 VCEP PP3 rule states: 'Missense: Do not use.' The only applicable PP3 path is for splicing predictions (SpliceAI ≥ 0.2), and this variant has a SpliceAI max delta score of 0.00, indicating no predicted splicing impact. REVEL score is 0.046 and BayesDel score is -0.707777, both leaning toward benign, but in silico missense predictors are not to be used per VCEP. Details ▾Hide ▴
Evidence considered
- VCEP PP3: 'Missense: Do not use.'
- SpliceAI max delta = 0.00 (no splicing impact).
- REVEL = 0.046 (not used per VCEP).
- BayesDel = -0.707777 (not used per VCEP).
Sources
BP4 N/AThe PALB2 VCEP BP4 rule explicitly states: 'Missense: Do not use.' The splicing component of BP4 (SpliceAI ≤ 0.1 with no predicted splicing impact) is not to be applied for missense variants per the VCEP. REVEL (0.046) and BayesDel (-0.707777) are not used because published predictors have not been validated for PALB2 missense functional outcome. Details ▾Hide ▴
Evidence considered
- VCEP BP4: 'Missense: Do not use.'
- SpliceAI max delta = 0.00 is consistent with no splicing impact but BP4 is not to be applied for missense.
- REVEL = 0.046
- BayesDel = -0.707777 (not used per VCEP).
Sources
BP7 N/ABP7 applies to synonymous and deep intronic variants. NM_024675.4:c.1096A>G is a missense variant (p.Asn366Asp) and does not qualify for BP7 under standard ACMG/AMP guidelines or the PALB2 VCEP. 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 = 0.046. BayesDel score = -0.707777.
6 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
-
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.Richards et al. (2015) ACMG/AMP standards and guidelines for the interpretation of sequence variants. This is the foundational framework document describing the variant classification criteria system. NM_024675.4:c.1096A>G was not identified in this paper.Does not name this variant
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PMID 24366376 ↗Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women: U.S. Preventive Services Task Force recommendation statement.Moyer VA et al. · 2014Moyer VA, U.S. Preventive Services Task Force (2014) recommendation statement on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in women. Focuses on BRCA1/BRCA2 testing recommendations. NM_024675.4:c.1096A>G was not identified.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 genetic risk assessment for BRCA-related breast or ovarian cancer. NM_024675.4:c.1096A>G was not identified.Does not name this variant
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PMID 24432435 ↗PMID 24432435Nelson HD et al. · 2013No paper-specific finding is recorded.
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PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015Hampel et al. (2015) practice guideline from ACMG and NSGC on referral indications for cancer predisposition assessment. Provides referral criteria for hereditary cancer syndromes including HBOC. NM_024675.4:c.1096A>G was not identified in this paper.Does not name this variant
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PMID 26389258 ↗Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version.PDQ Cancer Genetics Editorial Board · 2002PDQ Cancer Genetics Editorial Board (2002, updated periodically) summary on cancer genetics risk assessment and counseling. NM_024675.4:c.1096A>G was not identified.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
8 / 1,614,152 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
5 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/188117/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/16-23646771-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr16-23635450-T-C?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/16-23635450-T-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_024675.4%3Ac.1096…
- OncoKB ↗www.oncokb.org/gene/PALB2/N366D
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=PALB2+c.1096A%3EG
- 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= 4.95616e-06; MAF= 0.00050%, 8/1614152 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 8.78272e-05; MAF= 0.00878%, 8/91088 alleles, homozygotes = 0); grpmax FAF= 4.368e-05.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (5 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 188117)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.046. BayesDel score = -0.707777.
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.