About PALB2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PALB2 c.3049G>A, p.(Ala1017Thr)
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
The PALB2 VCEP BP1_Supporting applies to ALL PALB2 missense variants. Per the VCEP: 'Based on published and unpublished functional studies, PALB2 has a low rate of missense variants that are non-functional in relevant assays.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_024675.3:c.3049G>A is a missense variant (p.Ala1017Thr) and therefore qualifies for BP1 at Supporting strength.
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
13 / 1,614,106 alleles
gnomAD v4.1: 13 / 1,614,106 alleles. Recorded AF 8.05399e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.97697e-06; MAF= 0.00040%, 1/251448 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.26627e-05; MAF= 0.00327%, 1/30616 alleles, homozygotes = 0).
No listed criterion applied
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
7 reported laboratory submissions
7 Uncertain significance.
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 · 4 not met · 3 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_024675.3:c.3049G>A (p.Ala1017Thr) is a missense variant in PALB2, a gene for which loss of function is an established mechanism of PALB2-related cancer predisposition (autosomal dominant) and Fanconi anemia complementation group N (autosomal recessive).
This variant has been classified as a Variant of Uncertain Significance by the ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel (ClinVar Variation ID: 830187) and by seven clinical laboratories.
In gnomAD v4.1, this variant is present at an overall allele frequency of 0.000081% (13/1,614,106 alleles; grpmax FAF=0.0075%), with the highest frequency in the South Asian population (0.0132%; 12/91,078 alleles). The gnomAD v2.1 frequency is 0.00040% (1/251,448 alleles).
SpliceAI predicts no splicing impact (max delta score = 0.00). REVEL score is 0.202 and BayesDel score is -0.306, both in ranges consistent with a benign computational prediction, though in silico predictors are not used for missense variants under the PALB2 VCEP framework.
Under the PALB2 VCEP v1.2.0 framework, BP1 (Supporting) is met because all PALB2 missense variants are assigned BP1 at Supporting strength, given the very low rate of functional missense variants in PALB2. No other criteria are met under this VCEP framework.
The PM2 (Supporting) criterion is not met because the variant's gnomAD v4.1 frequency (0.00081%) exceeds the VCEP threshold of ≤0.000333%. Population frequency criteria BA1 (>0.1%) and BS1 (>0.01%) are also not met, as the grpmax FAF (0.0075%) falls below both thresholds.
PS4 is not met; although this variant has been observed in 3 cancer cases in a case-control study (Momozawa et al. 2018), no formal odds ratio or statistical significance test meeting the VCEP threshold (OR≥3, p≤0.05) has been computed for this individual variant.
Many ACMG/AMP criteria are not applicable under the PALB2 VCEP for missense variants, including PVS1 (not a null variant), PS1/PP3/BP4 (missense excluded), PM1 (missense mechanism not confirmed), PM5 (truncation/splice only), PP2 (missense mechanism not confirmed), and PS3/BS3 (not used in this VCEP).
Several criteria (PP1, BS2, BS4) remain not assessed due to absence of published co-segregation, healthy adult proband, or non-segregation data for this specific variant.
With only BP1_Supporting met and no pathogenic criteria met, this variant does not satisfy the criteria for Likely Benign (requires ≥2 benign supporting or 1 strong benign + ≥1 supporting benign). The variant remains classified as a Variant of Uncertain Significance (VUS) under the PALB2 VCEP v1.2.0 framework.
No criteria match.
Met · 1
BP1 SupportingThe PALB2 VCEP BP1_Supporting applies to ALL PALB2 missense variants. Per the VCEP: '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_024675.3:c.3049G>A is a missense variant (p.Ala1017Thr) and therefore qualifies for BP1 at Supporting strength. Details ▾Hide ▴
Evidence considered
- Missense variant in PALB2
- VCEP BP1 applies to all PALB2 missense variants at Supporting strength.
Sources
Not met · 4 · evaluated, threshold not reached
PS4 The PALB2 VCEP PS4 requires formal case-control statistics (p-value ≤0.05 AND odds ratio/relative risk ≥3 OR lower 95% CI ≥1.5). This variant has been observed in 2 breast cancer and 1 prostate cancer cases in Momozawa et al. (2018) with absence from 11,279 controls, but no formal odds ratio or statistical test has been computed for this individual variant. Raw case counts are insufficient to meet the VCEP threshold. The VCEP also withholds PS4_Moderate for proband counting. Details ▾Hide ▴
Evidence considered
- Observed in 3 cancer cases (2 breast
- 1 prostate) in Momozawa et al. 2018 but lacking formal case-control statistics
- gnomAD v4 frequency is very low (AF=0.000081%).
Still missing
- No formal case-control odds ratio or statistical enrichment analysis for this variant.
Sources
PM2 The PALB2 VCEP PM2_Supporting requires a frequency ≤1/300,000 (0.000333%) in gnomAD v4. In gnomAD v4.1, this variant has an overall allele frequency of 0.00081% (13/1,614,106 alleles), which exceeds the PM2 threshold. The variant is concentrated in the South Asian population (AF=0.0132%, 12/91,078). Per VCEP guidance, PM2 is not considered a conflicting piece of evidence for variants otherwise leaning benign. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 13/1
- 614
- 106 alleles (AF=0.00081%)
- exceeding PM2 threshold of ≤0.000333%
- grpmax FAF=0.0075%.
Sources
BA1 The PALB2 VCEP BA1 (Stand Alone) requires a grpmax filtering allele frequency >0.1% in gnomAD v4. The grpmax FAF for this variant is 0.0075% (7.506e-05), which is well below the >0.1% threshold for BA1. The variant is too rare in population databases to meet this criterion. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF=0.0075%
- below BA1 threshold of >0.1%.
Sources
BS1 The PALB2 VCEP BS1 (Strong) requires a grpmax filtering allele frequency >0.01% in gnomAD v4. The grpmax FAF for this variant is 0.0075% (7.506e-05), which falls below the >0.01% threshold. The variant is not sufficiently common in population databases to meet BS1. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF=0.0075%
- below BS1 threshold of >0.01%.
Sources
Not assessed · 3 · no assessment recorded
PP1 No published co-segregation analysis for NM_024675.3:c.3049G>A with PALB2-related cancer predisposition has been identified in the literature. The PALB2 VCEP requires, for autosomal dominant disease, LOD ≥0.3 or Bayes Factor (LR) ≥2:1 for Supporting-level evidence, or for autosomal recessive disease, segregation in ≥1 affected relative. Without family segregation data, PP1 cannot be evaluated. Details ▾Hide ▴
Evidence considered
- No co-segregation data identified for this variant.
Still missing
- No published co-segregation analysis
- family-based datasets (e.g.
- CIMBA) may contain unpublished data.
Sources
BS2 The PALB2 VCEP BS2 is applicable for Fanconi anemia (recessive) but requires observation in healthy adult individuals who are not from population-based cohorts such as gnomAD. No published reports of NM_024675.3:c.3049G>A in confirmed healthy adults (outside gnomAD) have been identified. The variant is present in gnomAD (13 heterozygotes in v4.1) but these cannot be used for BS2 per VCEP rules. Details ▾Hide ▴
Evidence considered
- VCEP BS2 requires healthy adult probands outside population cohorts
- none identified. gnomAD observations not usable per VCEP.
Still missing
- No published reports of this variant in confirmed healthy adults meeting Fanconi Anemia BS2 table criteria.
Sources
BS4 No published analysis showing lack of segregation of NM_024675.3:c.3049G>A with disease in affected family members has been identified. The PALB2 VCEP BS4 requires quantitative co-segregation analysis (LOD ≤-1.28 for Strong, LOD ≤-0.32 for Supporting). Without family segregation data showing non-segregation, BS4 cannot be evaluated. Details ▾Hide ▴
Evidence considered
- No non-segregation/family data identified for this variant.
Still missing
- No familial non-segregation studies
- PALB2 registries may hold unpublished data.
Sources
Not applicable · 18· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable to missense variants. NM_024675.3:c.3049G>A is a missense substitution (p.Ala1017Thr) and does not fall into any null-variant bucket (nonsense, frameshift, canonical ±1,2 splice consensus) defined by the PALB2 VCEP PVS1 Decision Tree. The pvs1_variant_assessment confirms this variant does not qualify for generic PVS1. Details ▾Hide ▴
Evidence considered
- Missense variant
- not a predicted null variant per PVS1 decision tree.
Sources
pvs1_variant_assessmentcspec ↗
PS1 N/AThe PALB2 VCEP restricts PS1 to splicing changes (PALB2 PS1 Splicing table) and explicitly states 'Missense: Do not use.' This variant is a missense change with SpliceAI max delta score of 0.00, indicating no predicted splice impact. No pathogenic variant at the same amino acid with a different nucleotide change has been established. Details ▾Hide ▴
Evidence considered
- VCEP PS1 restricted to splicing
- variant is missense with SpliceAI=0.00.
Sources
PS2 VCEPThe PALB2 VCEP declares PS2 not applicable: 'Do not use for AD or AR disease: Informative de novo occurrences have not yet been observed and de novo AR conditions are unlikely to be informed by phase.' As breast cancer is relatively common, de novo is unlikely to inform autosomal dominant disease. Details ▾Hide ▴
PS3 VCEPThe PALB2 VCEP declares PS3 not applicable as a standalone criterion. Per VCEP instructions, functional evidence for PALB2 missense variants is not assessed under PS3; protein functional studies follow ATM-specific assay guidance and RNA studies use PVS1_O with curator-modulated strength. Details ▾Hide ▴
PM1 VCEPThe PALB2 VCEP declares PM1 not applicable: 'Do not use: Missense pathogenic variation in PALB2 is not yet confirmed as a mechanism of disease.' No mutational hotspot or critical functional domain has been validated for PALB2 missense variants. Details ▾Hide ▴
PM5 N/AThe PALB2 VCEP PM5_Supporting applies only to frameshifting or truncating variants with premature termination codons upstream of p.Tyr1183, or splice variants with NMD-prone PTCs upstream of p.Tyr1183. The VCEP explicitly states: 'Do not use for missense changes: Missense changes are not yet confirmed as a mechanism of disease for PALB2.' This variant is a missense change (p.Ala1017Thr). Details ▾Hide ▴
Evidence considered
- Missense variant
- VCEP PM5 restricted to truncation/splice variants upstream of p.Tyr1183.
Sources
cspec ↗pm5_candidates
PM6 VCEPThe PALB2 VCEP declares PM6 not applicable: 'Do not use for AD or AR disease: Informative de novo occurrences have not yet been observed and de novo AR conditions are unlikely to be informed by phase.' Details ▾Hide ▴
PP2 VCEPThe PALB2 VCEP declares PP2 not applicable: 'Do not use. Missense is not yet confirmed or refuted as a mechanism of disease for PALB2.' PP2 requires a gene where missense variants are a common mechanism of disease with a low rate of benign missense variation. Details ▾Hide ▴
PP3 N/AThe PALB2 VCEP PP3 explicitly states: 'Missense: Do not use.' PP3 for PALB2 is restricted to splicing predictions (SpliceAI ≥0.2) for silent, missense/in-frame, and intronic variants. Although SpliceAI delta is 0.00 for this variant, the PP3 criterion is not applicable to missense variants per VCEP rules regardless of splicing predictions. In silico protein predictors (REVEL=0.202, BayesDel=-0.305671) are not used under this VCEP. Details ▾Hide ▴
Evidence considered
- VCEP PP3 excludes missense
- SpliceAI=0.00
- REVEL=0.202
- BayesDel=-0.306.
Sources
PP4 VCEPThe PALB2 VCEP declares PP4 not applicable: 'Do not use for AD disorder as breast cancer is a disease with multiple genetic etiology (genetic heterogeneity) and there are no features that can readily distinguish hereditary from sporadic causes.' Details ▾Hide ▴
PP5 VCEPThe PALB2 VCEP declares PP5 'Not Applicable for this VCEP' as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. This criterion should not be used in PALB2 variant interpretation. Details ▾Hide ▴
BS3 VCEPThe PALB2 VCEP declares BS3 not applicable. Per VCEP instructions, functional studies showing no damaging effect are assessed under other criteria (BP7 for RNA studies). Details ▾Hide ▴
BP2 VCEPThe PALB2 VCEP declares BP2 not applicable. Observed in trans/cis phase data is assessed using the ATM PM3/BP2 table per VCEP instructions, but BP2 as a standalone criterion is not used for PALB2. Details ▾Hide ▴
BP4 N/AThe PALB2 VCEP BP4 explicitly states: 'Missense: Do not use. So far, published predictors have yet to achieve functional outcome for PALB2 missense variants.' Although SpliceAI delta is 0.00 (≤0.1) and computational scores are in the benign range (REVEL=0.202, BayesDel=-0.306), BP4 is not applied to missense variants in this VCEP framework. Details ▾Hide ▴
Evidence considered
- VCEP BP4 excludes missense
- SpliceAI=0.00
- REVEL=0.202
- BayesDel=-0.306.
Sources
BP5 VCEPThe PALB2 VCEP declares BP5 not applicable: 'Do not use: Cases with multiple pathogenic variants have been observed with no noticeable difference in phenotype (e.g. BRCA1 and BRCA2). In addition, PALB2 has moderate penetrance and will naturally occur with other pathogenic variants more frequently due to higher tolerance/presence in the general population.' Details ▾Hide ▴
BP6 VCEPThe PALB2 VCEP declares BP6 '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 ▴
BP7 N/AThe PALB2 VCEP BP7 Supporting applies to synonymous and deep intronic variants (further than +7 at donor and -21 at acceptor sites). NM_024675.3:c.3049G>A is a missense variant, not a synonymous or deep intronic change. BP7(RNA) applies only to silent substitutions with demonstrated lack of aberrant RNA defect, which does not apply to this missense variant. Details ▾Hide ▴
Evidence considered
- Missense variant
- VCEP BP7 restricted to synonymous and deep intronic variants.
Sources
PS5 N/APS5 is not enumerated in the PALB2 VCEP criteria, and its supporting counterpart PP5 is explicitly declared 'Not Applicable for this VCEP.' By extension, PS5 is not used in the PALB2 VCEP framework. Details ▾Hide ▴
Identifiers
- Gene
- PALB2
- Transcript
- NM_024675.3
- Coding (HGVS c.)
- NM_024675.3:c.3049G>A
- Protein (HGVS p.)
- NP_078951.2:p.(Ala1017Thr)
- GRCh38
- chr16:23621426 C>T
- GRCh37
- chr16:23632747 C>T
- ClinVar
- 830187
Gene diagram
Every interpreted variant in PALB2, mapped onto the exon structure of NM_024675.3. Select a row to find it on the plot.
PALB2NM_024675.3
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in PALB2
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
13 / 1,614,106 alleles
AF 8.05e-06 · 0 homozygotes · FAF 7.51e-05
gnomAD v2.1
1 / 251,448 alleles
AF 3.98e-06 · 0 homozygotes
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD v4.1
AF 8.1e-06 · 13 / 1,614,106 alleles · 0 hom · FAF 7.5e-05
| South Asian12 / 91,078 | 0.00013 |
| Remaining individuals1 / 62,508 | 1.6e-05 |
0 alternate alleles recorded in 8 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, Ashkenazi Jewish, African/African American, European (non-Finnish).
gnomAD v2.1
AF 4e-06 · 1 / 251,448 alleles · 0 hom
| South Asian1 / 30,616 | 3.3e-05 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Remaining individuals.
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 8.05399e-06; MAF= 0.00081%, 13/1614106 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000131755; MAF= 0.01318%, 12/91078 alleles, homozygotes = 0); grpmax FAF= 7.506e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.97697e-06; MAF= 0.00040%, 1/251448 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.26627e-05; MAF= 0.00327%, 1/30616 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.202
- BayesDel
- -0.306
How the predictions were used
PP3 N/AThe PALB2 VCEP PP3 explicitly states: 'Missense: Do not use.' PP3 for PALB2 is restricted to splicing predictions (SpliceAI ≥0.2) for silent, missense/in-frame, and intronic variants. Although SpliceAI delta is 0.00 for this variant, the PP3 criterion is not applicable to missense variants per VCEP rules regardless of splicing predictions. In silico protein predictors (REVEL=0.202, BayesDel=-0.305671) are not used under this VCEP. Details ▾Hide ▴
Evidence considered
- VCEP PP3 excludes missense
- SpliceAI=0.00
- REVEL=0.202
- BayesDel=-0.306.
Sources
BP4 N/AThe PALB2 VCEP BP4 explicitly states: 'Missense: Do not use. So far, published predictors have yet to achieve functional outcome for PALB2 missense variants.' Although SpliceAI delta is 0.00 (≤0.1) and computational scores are in the benign range (REVEL=0.202, BayesDel=-0.306), BP4 is not applied to missense variants in this VCEP framework. Details ▾Hide ▴
Evidence considered
- VCEP BP4 excludes missense
- SpliceAI=0.00
- REVEL=0.202
- BayesDel=-0.306.
Sources
BP7 N/AThe PALB2 VCEP BP7 Supporting applies to synonymous and deep intronic variants (further than +7 at donor and -21 at acceptor sites). NM_024675.3:c.3049G>A is a missense variant, not a synonymous or deep intronic change. BP7(RNA) applies only to silent substitutions with demonstrated lack of aberrant RNA defect, which does not apply to this missense variant. Details ▾Hide ▴
Evidence considered
- Missense variant
- VCEP BP7 restricted to synonymous and deep intronic variants.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.202. BayesDel score = -0.305671.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
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PMID 23977390 ↗Prevalence of PALB2 mutations in breast cancer patients in multi-ethnic Asian population in Malaysia and Singapore.Phuah SY et al. · 2013No paper-specific finding is recorded.
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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.No paper-specific finding is recorded.
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.No paper-specific finding is recorded.
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PMID 31586400 ↗A global functional analysis of missense mutations reveals two major hotspots in the PALB2 tumor suppressor.Rodrigue A et al. · 2019No paper-specific finding is recorded.
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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.No paper-specific finding is recorded.
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PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.Trepanier A et al. · 2004No paper-specific finding is recorded.
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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. · 2007No paper-specific finding is recorded.
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PMID 18163131 ↗The emerging landscape of breast cancer susceptibility.Stratton MR et al. · 2008No paper-specific finding is recorded.
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
13 / 1,614,106 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
7 Uncertain significance
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/830187/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/16-23632747-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr16-23621426-C-T?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_024675.3%3Ac.3049…
- OncoKB ↗www.oncokb.org/gene/PALB2/A1017T
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=PALB2+c.3049G%3EA
- 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= 8.05399e-06; MAF= 0.00081%, 13/1614106 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 0.000131755; MAF= 0.01318%, 12/91078 alleles, homozygotes = 0); grpmax FAF= 7.506e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.97697e-06; MAF= 0.00040%, 1/251448 alleles, homozygotes = 0) and has highest observed frequency in the South Asian population (AF= 3.26627e-05; MAF= 0.00327%, 1/30616 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Uncertain significance (7 clinical laboratories) and as Uncertain Significance by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 830187)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.202. BayesDel score = -0.305671.
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.