About PALB2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PALB2 c.1001A>G, p.(Tyr334Cys)
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. Based on published and unpublished functional studies, PALB2 has a low rate of missense variants that are non-functional, and true pathogenic missense variants are thought to be exceedingly rare.
Recorded classification: Uncertain significance
Richards et.al., 2015 - Combining rules v1.2.0 criteria-combination framework was evaluated deterministically with applied criteria: BP1 supporting; 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
121 / 1,613,326 alleles
gnomAD v4.1: 121 / 1,613,326 alleles. Recorded AF 7.50003e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000106259; MAF= 0.01063%, 30/282328 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.000386473; MAF= 0.03865%, 4/10350 alleles, homozygotes = 0); grpmax FAF= 0.00012362.
gnomAD-Canada
Not available in 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
19 reported laboratory submissions
9 Uncertain significance · 9 Likely benign · 1 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 v1.2.0, with the data and sources behind each one.
27 criteria with recorded statuses: 1 met · 5 not met · 2 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
PALB2 VCEP BP1_Supporting is applied as this is a missense variant; true pathogenic missense variants in PALB2 are thought to be exceedingly rare.
This variant is present in gnomAD v4.1 at an allele frequency of 0.000075 (121/1,613,326 alleles), which exceeds the VCEP PM2 threshold of 0.00000333 but does not meet BS1 (>0.01%) or BA1 (>0.1%) benign population thresholds.
The variant has been observed in multiple cohorts at frequencies comparable to population controls (Balia 2010: 1/95 cases and 1/50 controls; Catucci 2012: 1/96 cases; Hellebrand 2011: 1/818 cases classified as polymorphism).
In silico predictors REVEL (0.014) and BayesDel (-0.648) are consistent with a benign interpretation, though PALB2 VCEP does not apply PP3/BP4 for missense variants as published predictors have not achieved functional outcome prediction.
No pathogenic criteria are met. With only BP1_Supporting (benign supporting) applied, the overall classification under PALB2 VCEP v1.2.0 is Uncertain Significance (VUS).
No criteria match.
Met · 1
BP1 SupportingPALB2 VCEP BP1 applies to all missense variants. Based on published and unpublished functional studies, PALB2 has a low rate of missense variants that are non-functional, and true pathogenic missense variants are thought to be exceedingly rare. Details ▾Hide ▴
Evidence considered
- PALB2 VCEP BP1 rule: Apply to all missense variants
- p.Tyr334Cys is a missense substitution
Sources
Not met · 5 · evaluated, threshold not reached
PS4 No case-control study demonstrates significant statistical enrichment of this variant in affected individuals. The variant has been observed at comparable frequencies in cases and controls (Balia 2010: 1/95 cases and 1/50 controls, 0.5%). VCEP PS4 requires p≤0.05 AND (OR≥3 or lower 95% CI ≥1.5). Details ▾Hide ▴
Evidence considered
- Balia 2010: c.1001A>G observed in 1/95 Italian breast cancer families and 1/50 controls (0.5% frequency)
- Hellebrand 2011: variant found in 1/818 German familial cases
- classified as polymorphism
- Catucci 2012: variant observed in 1/96 Jewish high-risk cases
- Garcia 2020: variant identified in 1/52 Brazilian HBOC patients
- ACMG class 2 (likely benign)
Still missing
- No case-control study with statistical power to evaluate enrichment
Sources
PM2 gnomAD v4.1 allele frequency (7.50e-05, 0.0075%) exceeds the PALB2 VCEP PM2_Supporting threshold of ≤1/300,000 (0.000333%). The variant is approximately 22-fold more common than the VCEP-defined cutoff. Although VCEP uses PM2 as Supporting strength only, the frequency threshold is not met. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 121/1
- 613
- 326 alleles (AF = 7.50e-05 = 0.0075%)
- gnomAD v2.1: 30/282
- 328 alleles (AF = 0.000106 = 0.0106%)
- VCEP PM2 threshold: ≤ 1/300
- 000 (0.000333%)
- variant frequency exceeds this threshold
Sources
PP1 No co-segregation data available meeting VCEP thresholds (LOD≥0.3 or LR≥2:1 for AD). The variant was identified by Garcia 2020 (PMID:33134171) in patient ID85, but co-segregation analysis was not performed for this family; only LOH was evaluated. Details ▾Hide ▴
Evidence considered
- Garcia 2020: PALB2 c.1001A>G identified in patient ID85
- co-segregation was not performed for this family
- LOH was observed in tumor tissue but does not satisfy PP1 co-segregation requirements
Still missing
- No family co-segregation data (LOD scores or LR)
Sources
BA1 gnomAD v4.1 grpmax filtering allele frequency (6.725e-05, 0.006725%) does not exceed the PALB2 VCEP BA1 threshold of >0.1%. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 6.725e-05 (0.006725%)
- VCEP BA1 threshold: >0.1%
- not met
Sources
BS1 gnomAD v4.1 grpmax filtering allele frequency (6.725e-05, 0.006725%) does not exceed the PALB2 VCEP BS1 threshold of >0.01%. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 6.725e-05 (0.006725%)
- VCEP BS1 threshold: >0.01%
- not met
Sources
Not assessed · 2 · no assessment recorded
BS2 VCEP BS2 requires Fanconi Anemia proband point-table assessment (≥4 points for Strong, 2 for Moderate, 1 for Supporting). No FA-affected probands with this variant were identified in the available evidence. Details ▾Hide ▴
Evidence considered
- No Fanconi Anemia probands identified with this variant.
Still missing
- No FA BS2 point-table data available for this variant
Sources
BS4 VCEP BS4 requires quantitative co-segregation analysis with LOD or Bayes Factor values. No such analysis has been performed for this variant. Details ▾Hide ▴
Evidence considered
- No LOD scores or quantitative segregation analysis available.
Still missing
- Quantitative co-segregation data (LOD scores) not available
Sources
Not applicable · 19· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AMissense variant (p.Tyr334Cys); the PALB2 VCEP PVS1 decision tree applies only to null variants (nonsense, frameshift, canonical splice). Missense changes are not eligible for PVS1. Details ▾Hide ▴
Evidence considered
- Missense substitution
- variant bucket: other. Not a null variant type.
Sources
cspec ↗pvs1_variant_assessment
PS1 N/APALB2 VCEP PS1 rule applies to splicing variants only (PS1 Splicing table). VCEP explicitly states: 'Missense: Do not use. Missense changes are not yet confirmed as a mechanism of disease for PALB2.' Details ▾Hide ▴
Evidence considered
- PALB2 VCEP PS1 restricted to splicing variants
- this is a missense substitution.
Sources
PS2 VCEPPALB2 VCEP explicitly designates PS2 as Not Applicable. Informative de novo occurrences have not been observed for PALB2-associated autosomal dominant disease. Details ▾Hide ▴
PS3 VCEPPALB2 VCEP explicitly designates PS3 as Not Applicable. Well-established functional studies for PALB2 missense variants are not available. Details ▾Hide ▴
PM1 VCEPPALB2 VCEP: 'Do not use: Missense pathogenic variation in PALB2 is not yet confirmed as a mechanism of disease.' PM1 is explicitly not applicable. Details ▾Hide ▴
PM5 N/APALB2 VCEP: 'Do not use for missense changes: Missense changes are not yet confirmed as a mechanism of disease for PALB2.' PM5 under VCEP applies only to frameshifting/truncating variants upstream of p.Tyr1183 or splice variants with NMD-prone PVS1 RNA evidence. Details ▾Hide ▴
Evidence considered
- PM5 is a truncation-cutoff rule
- not applicable to missense variants.
Sources
cspec ↗pm5_candidates
PM6 VCEPPALB2 VCEP explicitly designates PM6 as Not Applicable. Informative de novo occurrences have not been observed for PALB2-associated conditions. Details ▾Hide ▴
PP2 VCEPPALB2 VCEP: 'Do not use. Missense is not yet confirmed or refuted as a mechanism of disease for PALB2.' Details ▾Hide ▴
PP3 N/APALB2 VCEP PP3 rule: 'Missense: Do not use.' Published in silico predictors have not achieved functional outcome prediction for PALB2 missense variants. SpliceAI delta = 0.00, confirming absence of predicted splice impact, but PP3 is not applied for missense per VCEP. Details ▾Hide ▴
Evidence considered
- VCEP PP3: Missense — Do not use
- SpliceAI max delta = 0.00 (no predicted splice impact)
- REVEL = 0.014
- BayesDel = -0.648 (both benign-leaning)
Sources
PP4 VCEPPALB2 VCEP: 'Do not use for AD disorder as breast cancer is a disease with multiple genetic etiology.' PP4 is explicitly Not Applicable. Details ▾Hide ▴
PP5 VCEPPALB2 VCEP: Not Applicable for this VCEP, as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BS3 VCEPPALB2 VCEP explicitly designates BS3 as Not Applicable. Details ▾Hide ▴
BP2 VCEPPALB2 VCEP explicitly designates BP2 as Not Applicable. Details ▾Hide ▴
BP3 VCEPVCEP states BP3 is Not Applicable; small in-frame losses are neither confirmed nor refuted as a mechanism of pathogenicity for PALB2, and this is a substitution variant. Details ▾Hide ▴
Evidence considered
- Trivially not applicable: substitution variant
- not an in-frame indel.
BP4 N/APALB2 VCEP BP4 rule: 'Missense: Do not use.' Published in silico predictors have not achieved functional outcome prediction for PALB2 missense variants. SpliceAI delta=0.00 confirms no predicted splice impact, but BP4 is explicitly not applicable for missense. Details ▾Hide ▴
Evidence considered
- VCEP BP4: Missense — Do not use
- SpliceAI max delta = 0.00
- REVEL = 0.014
- BayesDel = -0.648
Sources
BP5 VCEPPALB2 VCEP: 'Do not use: Cases with multiple pathogenic variants have been observed with no noticeable difference in phenotype... PALB2 has moderate penetrance and will naturally occur with other pathogenic variants more frequently.' Details ▾Hide ▴
BP6 VCEPPALB2 VCEP: Not Applicable for this VCEP, as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
BP7 N/APALB2 VCEP applies BP7 to synonymous and deep intronic variants (beyond +7 donor and -21 acceptor). This is a missense variant (p.Tyr334Cys) and is not eligible for BP7 under VCEP rules. Details ▾Hide ▴
Evidence considered
- VCEP BP7 restricted to synonymous/deep intronic variants
- this is a missense substitution.
Sources
PS5 N/APS5 is not defined in the PALB2 VCEP v1.2.0 criteria set. In ClinGen VCEP frameworks, PS5 is typically subsumed by other pathogenic criteria or not independently applied. Details ▾Hide ▴
Identifiers
- Gene
- PALB2
- Transcript
- NM_024675.4
- Coding (HGVS c.)
- NM_024675.4:c.1001A>G
- Protein (HGVS p.)
- NP_078951.2:p.(Tyr334Cys)
- GRCh38
- chr16:23635545 T>C
- GRCh37
- chr16:23646866 T>C
- ClinVar
- 126581
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
121 / 1,613,326 alleles
AF 7.5e-05 · 0 homozygotes · FAF 6.72e-05
gnomAD v2.1
30 / 282,328 alleles
AF 0.000106 · 0 homozygotes · FAF 0.000124
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 7.5e-05 · 121 / 1,613,326 alleles · 0 hom · FAF 6.7e-05
| Ashkenazi Jewish17 / 29,588 | 0.00057 |
| Remaining individuals6 / 62,438 | 9.6e-05 |
| European (non-Finnish)95 / 1,179,698 | 8.1e-05 |
| Admixed American2 / 59,856 | 3.3e-05 |
| South Asian1 / 91,040 | 1.1e-05 |
0 alternate alleles recorded in 5 other groups: European (Finnish), Amish, East Asian, Middle Eastern, African/African American.
gnomAD v2.1
AF 0.00011 · 30 / 282,328 alleles · 0 hom · FAF 0.00012
| Ashkenazi Jewish4 / 10,350 | 0.00039 |
| European (non-Finnish)23 / 128,918 | 0.00018 |
| Remaining individuals1 / 7,212 | 0.00014 |
| Admixed American2 / 35,334 | 5.7e-05 |
0 alternate alleles recorded in 4 other groups: African/African American, East Asian, European (Finnish), South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 7.50003e-05; MAF= 0.00750%, 121/1613326 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.000574557; MAF= 0.05746%, 17/29588 alleles, homozygotes = 0); grpmax FAF= 6.725e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000106259; MAF= 0.01063%, 30/282328 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.000386473; MAF= 0.03865%, 4/10350 alleles, homozygotes = 0); grpmax FAF= 0.00012362.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.014
- BayesDel
- -0.648
How the predictions were used
PP3 N/APALB2 VCEP PP3 rule: 'Missense: Do not use.' Published in silico predictors have not achieved functional outcome prediction for PALB2 missense variants. SpliceAI delta = 0.00, confirming absence of predicted splice impact, but PP3 is not applied for missense per VCEP. Details ▾Hide ▴
Evidence considered
- VCEP PP3: Missense — Do not use
- SpliceAI max delta = 0.00 (no predicted splice impact)
- REVEL = 0.014
- BayesDel = -0.648 (both benign-leaning)
Sources
BP4 N/APALB2 VCEP BP4 rule: 'Missense: Do not use.' Published in silico predictors have not achieved functional outcome prediction for PALB2 missense variants. SpliceAI delta=0.00 confirms no predicted splice impact, but BP4 is explicitly not applicable for missense. Details ▾Hide ▴
Evidence considered
- VCEP BP4: Missense — Do not use
- SpliceAI max delta = 0.00
- REVEL = 0.014
- BayesDel = -0.648
Sources
BP7 N/APALB2 VCEP applies BP7 to synonymous and deep intronic variants (beyond +7 donor and -21 acceptor). This is a missense variant (p.Tyr334Cys) and is not eligible for BP7 under VCEP rules. Details ▾Hide ▴
Evidence considered
- VCEP BP7 restricted to synonymous/deep intronic variants
- this is a missense substitution.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.014. BayesDel score = -0.648329.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Recorded publications
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PMID 22692731 ↗Germline mutations in BRIP1 and PALB2 in Jewish high cancer risk families.Catucci I et al. · 2012PALB2 c.1001A>G (p.Tyr334Cys) was identified in 1/96 Jewish high-risk breast/ovarian cancer cases (1 heterozygote, 95 wild-type). Previously reported variant; PolyPhen2/SIFT/SNPs&GO all predicted Benign/Tolerated/Neutral. No truncating PALB2 mutations were found.Names this variant
Quoted passage
c.1001A [ G... p.Tyr334Cys... Missense... Previously reported... 95/1/0... B/T/N
Table 2; Results section PALB2 genotyping
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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 2015 standards and guidelines for interpretation of sequence variants. General framework paper; does not discuss PALB2 or this specific variant.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.Population-based study of rare protein-truncating variants in ATM, CHEK2, and PALB2 in 13,087 breast cancer cases and 5,488 controls from East Anglia, UK. This specific missense variant was not reported or discussed.Does not name this variant
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PMID 33134171 ↗Using Co-segregation and Loss of Heterozygosity Analysis to Define the Pathogenicity of Unclassified Variants in Hereditary Breast Cancer Patients.PALB2 c.1001A>G (p.Tyr334Cys) was identified in patient ID85 (Brazilian HBOC cohort, n=52). ACMG classified as class 2 (likely benign). Loss of heterozygosity was observed in tumor tissue. Co-segregation analysis was not performed for this family. REVEL score 0.014; CADD 0.06.Names this variant
Quoted passage
the VUS in the gene PALB2 c.1001A>G, identified in ID85, showed LOH in the tumor.
Table 2; Results section Segregation and LOH Analysis; Discussion
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PMID 20301425 ↗BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.GeneReviews overview of BRCA1/BRCA2-associated hereditary breast and ovarian cancer. Does not discuss PALB2 c.1001A>G or the PALB2 gene in variant-specific detail.Does not name this variant
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PMID 20852946 ↗PALB2: a novel inactivating mutation in a Italian breast cancer family.Balia C et al. · 2010PALB2 c.1001A>G (p.Tyr334Cys, reported as c.1201A>G under NM_024675.3) was identified in 1/95 Italian familial breast cancer cases and in 1/50 healthy controls, with a frequency of 0.5% in both groups. PolyPhen predicted Benign; SIFT predicted Tolerated.Names this variant
Quoted passage
Y334C... frequency... was 0.5%, the same as found in the cases.
Table 1; Results paragraph 'mutational analysis'
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PMID 21618343 ↗Germline mutations in the PALB2 gene are population specific and occur with low frequencies in familial breast cancer.Hellebrand H et al. · 2011PALB2 c.1001A>G (p.Tyr334Cys) was identified in 1/818 German familial breast cancer cases. In silico predictions: PolyPhen benign, SIFT tolerated; classified as a polymorphism. Not found among the seven clearly pathogenic truncating mutations in this cohort.Names this variant
Quoted passage
c.1001A>G... Y334C... no... high... benign... tolerated... polymorphism
Supp. Table S2 (missense variants); line 703-709
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PMID 22241545 ↗Rare germline mutations in PALB2 and breast cancer risk: a population-based study.Tischkowitz M et al. · 2012Population-based case-control study (WECARE Study) of PALB2 rare variants in contralateral breast cancer. The paper focuses on truncating and rare missense variants but this specific variant was not identified or discussed.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Sherloc refinement of ACMG-AMP variant classification criteria. General methodology paper; does not discuss PALB2 or this specific variant.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
121 / 1,613,326 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
9 Uncertain significance · 9 Likely benign · 1 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/126581/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/16-23646866-T-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr16-23635545-T-C?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/16-23635545-T-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_024675.4%3Ac.1001…
- OncoKB ↗www.oncokb.org/gene/PALB2/Y334C
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=PALB2+c.1001A%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= 7.50003e-05; MAF= 0.00750%, 121/1613326 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.000574557; MAF= 0.05746%, 17/29588 alleles, homozygotes = 0); grpmax FAF= 6.725e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000106259; MAF= 0.01063%, 30/282328 alleles, homozygotes = 0) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.000386473; MAF= 0.03865%, 4/10350 alleles, homozygotes = 0); grpmax FAF= 0.00012362.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (9 clinical laboratories) and as Likely benign (9 clinical laboratories) and as Benign (1 clinical laboratory). (ClinVarID = 126581)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.014. BayesDel score = -0.648329.
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.