About PALB2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PALB2 c.205C>T, p.(His69Tyr)
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 specifies application to all missense variants in PALB2. Based on published and unpublished functional studies, PALB2 has a low rate of missense variants that are non-functional in relevant assays, and true pathogenic missense variants are thought to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 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
2 / 1,609,786 alleles
gnomAD v4.1: 2 / 1,609,786 alleles. Recorded AF 1.2424e-06. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
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
8 reported laboratory submissions
6 Uncertain significance · 2 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.
26 criteria with recorded statuses: 1 met · 7 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.205C>T (p.His69Tyr) is a missense variant in PALB2 exon 3. Under the ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Expert Panel specification for PALB2 v1.2.0, missense variants are not a confirmed mechanism of disease.
BP1_Supporting is met: the VCEP applies BP1 to all PALB2 missense variants given the very low likelihood that missense variants are pathogenic.
PM2_Supporting is not applied: while the overall gnomAD v4.1 frequency (0.000124%) is below the VCEP threshold (≤0.000333%), the variant is observed in the East Asian subpopulation at 0.00223% (1/44,858 alleles), triggering the VCEP exception for under-represented sub-populations with frequency >0.0003%.
The variant is present in gnomAD v4.1 at extremely low frequency (2/1,609,786 alleles; 0 homozygotes). It is absent from gnomAD v2.1.
This variant has been reported in ClinVar (ID 245654) as Uncertain significance by 6 clinical laboratories and Likely benign by 2 clinical laboratories. No expert panel classification is available.
SpliceAI predicts no splicing impact (max delta score 0.00). REVEL (0.053) and BayesDel (-0.387659) are consistent with a benign computational prediction, though in silico predictors are not used for PALB2 missense variants under this VCEP.
Multiple criteria are not applicable under the PALB2 VCEP for missense variants: PVS1 (not a null variant), PS1 (missense excluded), PM1 (missense pathogenicity not confirmed), PM5 (missense excluded), PP2 (missense not confirmed), PP3 (missense excluded), BP4 (missense excluded), BP7 (missense excluded). PS2, PM6, PS3, BS3, PP4, PP5, BP2, BP5, BP6 are not applicable per VCEP specification.
No variant-specific functional, segregation, case-control, or Fanconi Anemia proband data were identified in the reviewed literature or databases.
No criteria match.
Met · 1
BP1 SupportingPALB2 VCEP BP1 specifies application to all missense variants in PALB2. Based on published and unpublished functional studies, PALB2 has a low rate of missense variants that are non-functional in relevant assays, and true pathogenic missense variants are thought to be exceedingly rare. Details ▾Hide ▴
Evidence considered
- VCEP BP1: 'Apply to all missense variants' — BP1_Supporting assigned automatically
- PALB2 missense pathogenic variants not confirmed as a mechanism of disease
Sources
Not met · 7 · evaluated, threshold not reached
PS4 No case-control study meeting the PALB2 VCEP threshold (p≤0.05 and OR≥3 or lower 95% CI≥1.5) was identified for this variant. The variant has been observed in ClinVar with 6 laboratories reporting VUS and 2 reporting likely benign, but proband counting alone is insufficient under the VCEP which requires calibrated case-control data. Details ▾Hide ▴
PM2 The variant is present in gnomAD v4.1 at very low frequency (AF=0.000124%, 2/1,609,786 alleles), which is below the PALB2 VCEP PM2_Supporting threshold of ≤0.000333%. However, the variant is observed in the East Asian subpopulation at AF=0.00223% (1/44,858 alleles), which triggers the VCEP exception for under-represented sub-populations with n=1 but frequency >0.0003%. PM2 is therefore not applied. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: total AF=1.24e-6 (2/1
- 609
- 786 alleles
- 0 homozygotes)
- East Asian subpopulation: AC=1
- AN=44
- 858
- AF=2.23e-5 (0.00223%)
- Admixed American subpopulation: AC=1
- AN=60
- 014
- AF=1.67e-5 (0.00167%)
- VCEP PM2_Supporting threshold: ≤0.000333% overall
- exception triggered by EAS subpopulation frequency >0.0003%
Sources
PP1 No co-segregation data (LOD scores, Bayes factors, or affected relative counts) were identified for this variant. The PALB2 VCEP requires quantitative co-segregation analysis; no such data are available. Details ▾Hide ▴
Evidence considered
- No segregation analysis (LOD
- Bayes factor
- or affected relative counts) identified in literature or ClinVar submissions for this variant
Still missing
- No co-segregation or family study data available
Sources
BA1 The variant does not meet the PALB2 VCEP BA1 threshold of Grpmax Filtering AF >0.1% in gnomAD v4. The total allele frequency is 0.000124% (2/1,609,786 alleles). Grpmax filtering AF is not available, but even the highest subpopulation frequency (East Asian, 0.00223%) is well below the 0.1% threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: total AF=1.24e-6 (0.000124%)
- highest subpopulation AF=2.23e-5 (0.00223%)
- VCEP BA1 threshold: Grpmax Filtering AF >0.1% — not met
Sources
BS1 The variant does not meet the PALB2 VCEP BS1 threshold of Grpmax Filtering AF >0.01% in gnomAD v4. The highest subpopulation frequency (East Asian) is 0.00223%, below the 0.01% threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: highest subpopulation AF=2.23e-5 (0.00223% in East Asian)
- VCEP BS1 threshold: Grpmax Filtering AF >0.01% — not met
Sources
BS2 No Fanconi Anemia proband data are available to assign BS2 points under the PALB2 VCEP BS2 tables. BS2 requires observation in healthy individuals with specific Fanconi Anemia phenotypic context, which is absent from the available evidence. Details ▾Hide ▴
Evidence considered
- VCEP BS2: requires Fanconi Anemia proband point assignment (≥4 for Strong
- 2 for Moderate
- 1 for Supporting)
- No FA proband data identified for this variant
Still missing
- No Fanconi Anemia proband or healthy control data available
Sources
BS4 No quantitative co-segregation data (LOD scores or Bayes factors) demonstrating lack of segregation are available for this variant. The PALB2 VCEP mandates quantitative analysis for BS4 assessment. Details ▾Hide ▴
Evidence considered
- VCEP BS4: requires LOD ≤ -1.28 (Strong)
- ≤ -0.64 (Moderate)
- or ≤ -0.32 (Supporting)
- No segregation data available for this variant
Still missing
- No co-segregation or family study data available
Sources
Not applicable · 18· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/ANM_024675.4:c.205C>T is a missense variant (p.His69Tyr). The PALB2 VCEP PVS1 decision tree (v1.2.0) applies to null variants (nonsense, frameshift, canonical splice). Generic PVS1 framework confirms this variant falls outside null-variant buckets. Details ▾Hide ▴
Evidence considered
- Missense substitution at codon 69 (His→Tyr)
- exon 3 of 13
- VCEP PVS1 decision tree restricted to null variants: nonsense
- frameshift
- canonical ±1
- 2 splice
- Generic PVS1 framework (PMC6185798): variant classified as 'other'
- not null-variant bucket
Sources
PS1 N/APALB2 VCEP PS1 specifies 'Missense: Do not use. Missense changes are not yet confirmed as a mechanism of disease for PALB2.' PS1 under this VCEP is restricted to splicing variants via the PALB2 PS1 Splicing table (PMID:37352859). Details ▾Hide ▴
Evidence considered
- VCEP PS1 rule: missense explicitly excluded
- splicing-only framework
- This is a missense variant (p.His69Tyr)
Sources
PS2 VCEPPALB2 VCEP specifies PS2 as not applicable: 'Do not use for AD or AR disease: Informative de novo occurrences have not yet been observed.' Details ▾Hide ▴
Evidence considered
- VCEP PS2: not applicable for autosomal dominant or recessive PALB2-associated conditions
Sources
PS3 VCEPPALB2 VCEP specifies PS3 as not applicable for protein-level functional assays. Functional assessment for PALB2 missense variants is directed to RNA-level evidence under PVS1/BP7 frameworks. Details ▾Hide ▴
Evidence considered
- VCEP PS3: not applicable
- protein functional studies not validated for PALB2 missense pathogenicity
Sources
PM1 VCEPPALB2 VCEP specifies PM1 as not applicable: 'Do not use: Missense pathogenic variation in PALB2 is not yet confirmed as a mechanism of disease.' Details ▾Hide ▴
Evidence considered
- VCEP PM1: not applicable
- missense pathogenicity not confirmed in PALB2
Sources
PM5 N/APALB2 VCEP PM5 specifies: 'Do not use for missense changes: Missense changes are not yet confirmed as a mechanism of disease for PALB2.' The applicable PM5 rule is restricted to frameshifting/truncating variants upstream of p.Tyr1183 and splice variants, which does not apply to this missense variant. Details ▾Hide ▴
Evidence considered
- VCEP PM5: missense excluded
- rule applies only to truncating/frameshifting variants upstream of p.Tyr1183
- pm5_candidates.json: recommendation level = not_applicable
- not a classic same-residue missense PM5
Sources
cspec ↗pm5_candidates
PM6 VCEPPALB2 VCEP specifies PM6 as not applicable: 'Do not use for AD or AR disease: Informative de novo occurrences have not yet been observed.' Details ▾Hide ▴
Evidence considered
- VCEP PM6: not applicable
- de novo occurrences not observed for PALB2-associated conditions
Sources
PP2 VCEPPALB2 VCEP specifies PP2 as not applicable: 'Do not use. Missense is not yet confirmed or refuted as a mechanism of disease for PALB2.' Details ▾Hide ▴
Evidence considered
- VCEP PP2: not applicable
- missense variant pathogenicity not established in PALB2
Sources
PP3 N/APALB2 VCEP PP3 specifies: 'Missense: Do not use.' PP3 under this VCEP is restricted to splicing variants with SpliceAI ≥0.2. This is a missense variant (p.His69Tyr). REVEL score is 0.053 and BayesDel score is -0.387659, both consistent with a benign in silico prediction, but computational predictors are not used for PALB2 missense variants under this VCEP. Details ▾Hide ▴
Evidence considered
- VCEP PP3: missense excluded
- splicing-only with SpliceAI ≥0.2 threshold
- SpliceAI max delta score: 0.00 (no predicted splicing impact)
- REVEL: 0.053
- BayesDel: -0.387659 (both predict benign
- but not used per VCEP)
Sources
PP4 VCEPPALB2 VCEP specifies PP4 as not applicable: breast cancer has multiple genetic etiologies and no features readily distinguish hereditary from sporadic causes under this criterion. Details ▾Hide ▴
Evidence considered
- VCEP PP4: not applicable for autosomal dominant PALB2-related cancer predisposition
Sources
PP5 VCEPPALB2 VCEP specifies PP5 as 'Not Applicable for this VCEP' per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation. Details ▾Hide ▴
Evidence considered
- VCEP PP5: not for use under this VCEP per ClinGen SVI VCEP Review Committee
Sources
BS3 VCEPPALB2 VCEP specifies BS3 as not applicable for protein-level functional studies. Benign functional evidence for PALB2 missense variants is assessed under the BP7(RNA) framework. Details ▾Hide ▴
BP2 VCEPPALB2 VCEP specifies BP2 as not applicable. Details ▾Hide ▴
BP4 N/APALB2 VCEP BP4 specifies: 'Missense: Do not use.' BP4 under this VCEP is restricted to splicing variants with SpliceAI ≤0.1. This is a missense variant (p.His69Tyr). Details ▾Hide ▴
Evidence considered
- VCEP BP4: missense excluded
- splicing-only with SpliceAI ≤0.1 threshold
- SpliceAI max delta score: 0.00 (no predicted splicing impact
- but not applied per VCEP missense exclusion)
Sources
BP5 VCEPPALB2 VCEP specifies BP5 as not applicable: cases with multiple pathogenic variants have been observed in PALB2 with no noticeable phenotypic difference, and PALB2 moderate penetrance means co-occurrence with other pathogenic variants is not informative. Details ▾Hide ▴
BP6 VCEPPALB2 VCEP specifies BP6 as 'Not Applicable for this VCEP' per ClinGen Sequence Variant Interpretation VCEP Review Committee recommendation. Details ▾Hide ▴
Evidence considered
- VCEP BP6: not for use under this VCEP per ClinGen SVI VCEP Review Committee
Sources
BP7 N/APALB2 VCEP BP7 applies to synonymous and deep intronic variants. The Supporting strength rule specifies: 'Use for synonymous and deep intronic variants defined as further than (but not including) +7 and further than (but not including) -21 at donor and acceptor sites.' This is a missense variant (p.His69Tyr). Details ▾Hide ▴
Evidence considered
- VCEP BP7: restricted to synonymous and deep intronic variants
- missense not eligible
- Variant is a missense substitution (c.205C>T
- p.His69Tyr)
Sources
PS5 N/APS5 is not a recognized criterion in the ACMG/AMP 2015 framework (PMID:25741868) or the PALB2 VCEP v1.2.0 specification. Details ▾Hide ▴
Evidence considered
- PS5 does not exist in standard ACMG/AMP or PALB2 VCEP criteria
Identifiers
- Gene
- PALB2
- Transcript
- NM_024675.4
- Coding (HGVS c.)
- NM_024675.4:c.205C>T
- Protein (HGVS p.)
- NP_078951.2:p.(His69Tyr)
- GRCh38
- chr16:23637856 G>A
- GRCh37
- chr16:23649177 G>A
- ClinVar
- 245654
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
2 / 1,609,786 alleles
AF 1.24e-06 · 0 homozygotes
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.2e-06 · 2 / 1,609,786 alleles · 0 hom
| East Asian1 / 44,858 | 2.2e-05 |
| Admixed American1 / 60,014 | 1.7e-05 |
0 alternate alleles recorded in 8 other groups: Remaining individuals, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish).
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.2424e-06; MAF= 0.00012%, 2/1609786 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.22926e-05; MAF= 0.00223%, 1/44858 alleles, homozygotes = 0).
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Not available in gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.053
- BayesDel
- -0.388
How the predictions were used
PP3 N/APALB2 VCEP PP3 specifies: 'Missense: Do not use.' PP3 under this VCEP is restricted to splicing variants with SpliceAI ≥0.2. This is a missense variant (p.His69Tyr). REVEL score is 0.053 and BayesDel score is -0.387659, both consistent with a benign in silico prediction, but computational predictors are not used for PALB2 missense variants under this VCEP. Details ▾Hide ▴
Evidence considered
- VCEP PP3: missense excluded
- splicing-only with SpliceAI ≥0.2 threshold
- SpliceAI max delta score: 0.00 (no predicted splicing impact)
- REVEL: 0.053
- BayesDel: -0.387659 (both predict benign
- but not used per VCEP)
Sources
BP4 N/APALB2 VCEP BP4 specifies: 'Missense: Do not use.' BP4 under this VCEP is restricted to splicing variants with SpliceAI ≤0.1. This is a missense variant (p.His69Tyr). Details ▾Hide ▴
Evidence considered
- VCEP BP4: missense excluded
- splicing-only with SpliceAI ≤0.1 threshold
- SpliceAI max delta score: 0.00 (no predicted splicing impact
- but not applied per VCEP missense exclusion)
Sources
BP7 N/APALB2 VCEP BP7 applies to synonymous and deep intronic variants. The Supporting strength rule specifies: 'Use for synonymous and deep intronic variants defined as further than (but not including) +7 and further than (but not including) -21 at donor and acceptor sites.' This is a missense variant (p.His69Tyr). Details ▾Hide ▴
Evidence considered
- VCEP BP7: restricted to synonymous and deep intronic variants
- missense not eligible
- Variant is a missense substitution (c.205C>T
- p.His69Tyr)
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.053. BayesDel score = -0.387659.
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.Standards and guidelines for the interpretation of sequence variants (ACMG/AMP 2015). Provides the generic ACMG/AMP classification framework. NM_024675.4:c.205C>T (p.His69Tyr) was not mentioned in this paper.Does not name this variant
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Standardized DNA variant scoring system for pathogenicity assessments in Mendelian disorders (Karbassi et al., 2016). Describes a rules-based scoring methodology. NM_024675.4:c.205C>T (p.His69Tyr) was not mentioned in this paper.Does not name this variant
-
PMID 34326862 ↗Analysis of Sequence and Copy Number Variants in Canadian Patient Cohort With Familial Cancer Syndromes Using a Unique Next Generation Sequencing Based Approach.Bhai P et al. · 2021Analysis of sequence and copy number variants in a Canadian patient cohort with familial cancer syndromes (Bhai et al., 2021). Reports aggregate PALB2 pathogenic variant frequencies (1% in breast cancer, 0.4% in ovarian cancer, 8.3% in pancreatic cancer) but does not enumerate individual VUS or list NM_024675.4:c.205C>T (p.His69Tyr) specifically.Does not name this variant
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PMID 20301425 ↗BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer.Adam MP et al. · 1993BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer (GeneReviews). General reference on BRCA-related cancer genetics. Abstract and full text not available for review; no indication the specific PALB2 variant c.205C>T is discussed.Does not name this variant
-
PMID 24432435 ↗PMID 24432435No paper-specific finding is recorded.
-
PMID 26389258 ↗Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional VersiCancer Genetics Risk Assessment and Counseling (PDQ Health Professional Version). General reference on cancer genetics counseling. Abstract and full text not available for review; no indication the specific PALB2 variant c.205C>T is discussed.Does not name this variant
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PMID 31429903 ↗Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: US Preventive Services Task Force Recommendation Statement.USPSTF recommendation statement on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer (2019). Mentions PALB2 in passing in the context of expanded gene panels. NM_024675.4:c.205C>T (p.His69Tyr) was not mentioned in this paper.Does not name this variant
-
PMID 31479213 ↗PMID 31479213No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
2 / 1,609,786 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 · 2 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/245654/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/16-23649177-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr16-23637856-G-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/16-23637856-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_024675.4%3Ac.205C…
- OncoKB ↗www.oncokb.org/gene/PALB2/H69Y
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=PALB2+c.205C%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= 1.2424e-06; MAF= 0.00012%, 2/1609786 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 2.22926e-05; MAF= 0.00223%, 1/44858 alleles, homozygotes = 0).
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 (6 clinical laboratories) and as Likely benign (2 clinical laboratories). (ClinVarID = 245654)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.053. BayesDel score = -0.387659.
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.