About PALB2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PALB2 c.1684+1G>A, p.?
Classification
Pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.
Pathogenic.A pathogenic classification under the recorded framework.
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: 3
Benign evidence criteria: 0
Pathogenic criteria applied · 3
PVS1Very strong
PVS1 · very strong
NM_024675.3:c.1684+1G>A is a canonical +1 donor splice site variant in PALB2, a gene for which loss of function is an established mechanism for hereditary breast, ovarian, and pancreatic cancer predisposition (monoallelic) and Fanconi anemia subtype FA-N (biallelic). The ClinGen PALB2 VCEP v1.2.0 PVS1 decision tree applies. RNA analysis of this variant has been performed and reported (Lopez-Perolio et al., 2019, PMID:30890586), confirming aberrant splicing. Under the PALB2 VCEP framework, PVS1_VeryStrong is assigned for a canonical splice site variant with observed RNA-level splice defect in a gene where LOF is a known disease mechanism.
PM2Supporting
PM2 · supporting
NM_024675.3:c.1684+1G>A is absent from gnomAD v2.1 and v4.1. Under the PALB2 VCEP v1.2.0, PM2 is applied at Supporting strength (not Moderate) when the variant frequency is ≤0.000333% (1/300,000) in gnomAD v4. The variant meets this threshold as it is completely absent from both gnomAD datasets.
PM5Supporting
PM5 · supporting
Under the PALB2 VCEP v1.2.0, PM5_Supporting is applied to splice variants with premature termination codons upstream of p.Tyr1183 when PVS1_VS(RNA) is applied based on high-quality observed splicing impact and the variant is NMD-prone. NM_024675.3:c.1684+1G>A is a canonical +1 splice site variant in intron 4 that has been shown to cause aberrant splicing by RNA analysis (PMID:30890586). The resulting transcript is predicted to introduce a premature termination codon far upstream of the p.Tyr1183 boundary and is expected to be NMD-prone, satisfying the VCEP PM5_Supporting conditions.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Pathogenic
Richards et.al., 2015 - Combining rules v1.2.0 criteria-combination framework: matched Rule4 (1 Pathogenic.Very Strong + Pathogenic.Supporting >=2) with applied criteria: PVS1 very strong, PM2 supporting, PM5 supporting; maps to Pathogenic.
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
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
Absent from gnomAD v2.1.
SpliceAI score
0.940 maximum delta
Recorded SpliceAI maximum delta score: 0.940. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
3 reported laboratory submissions
2 Likely pathogenic · 1 Pathogenic.
Context only
ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
OncoKB ↗
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Context only
COSMIC ↗
For specialists
Technical detail
ACMG/AMP criteria under ClinGen PALB2 VCEP v1.2.0, with the data and sources behind each one.
29 criteria with recorded statuses: 3 met · 10 not met · 1 not assessed · 15 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.1684+1G>A is a canonical +1 donor splice site variant in intron 4 of PALB2, a gene for which loss of function is an established mechanism for hereditary breast, ovarian, and pancreatic cancer predisposition (ClinGen PALB2 VCEP v1.2.0).
This variant is absent from gnomAD v2.1 and v4.1 population databases, satisfying the PALB2 VCEP PM2_Supporting threshold of ≤0.000333% allele frequency (PM2_Supporting).
RNA analysis performed by Lopez-Perolio et al. (2019, PMID:30890586) confirmed aberrant splicing for c.1684+1G>A, supporting classification as a null variant under the PALB2 VCEP PVS1 decision tree at Very Strong strength (PVS1).
The variant introduces a premature termination codon upstream of p.Tyr1183 and is predicted to be NMD-prone; combined with RNA-confirmed splice defect, PM5_Supporting is applied per PALB2 VCEP rules (PM5_Supporting).
No benign criteria are met: the variant is not present at significant population frequency (BA1/BS1 not met), SpliceAI predicts a strong splice impact (BP4 not met), the variant is not at a position eligible for BP7, and no evidence of normal splicing or lack of segregation is available.
Applying the ACMG/AMP combination rules (Richards et al. 2015) as adopted by the PALB2 VCEP: 1 Pathogenic Very Strong (PVS1) + ≥2 Pathogenic Supporting (PM2_Supporting, PM5_Supporting) yields a classification of Pathogenic under Rule 4.
Note: The ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer VCEP classifies this variant as Uncertain Significance (ClinVar ID 482029). The discrepancy between the automated adjudication (Pathogenic) and the expert panel classification (VUS) may reflect additional VCEP-specific PVS1 decision tree nuances, PS1 splicing table consultation, or clinical judgment not fully captured in the available evidence materials. Human review by a PALB2 VCEP curator is recommended.
No criteria match.
Met · 3
PVS1 Very strongNM_024675.3:c.1684+1G>A is a canonical +1 donor splice site variant in PALB2, a gene for which loss of function is an established mechanism for hereditary breast, ovarian, and pancreatic cancer predisposition (monoallelic) and Fanconi anemia subtype FA-N (biallelic). The ClinGen PALB2 VCEP v1.2.0 PVS1 decision tree applies. RNA analysis of this variant has been performed and reported (Lopez-Perolio et al., 2019, PMID:30890586), confirming aberrant splicing. Under the PALB2 VCEP framework, PVS1_VeryStrong is assigned for a canonical splice site variant with observed RNA-level splice defect in a gene where LOF is a known disease mechanism. Details ▾Hide ▴
Evidence considered
- Canonical +1 donor splice site (intron 4) in PALB2
- PALB2 loss-of-function is established disease mechanism for breast/ovarian/pancreatic cancer and Fanconi anemia
- ClinGen PALB2 VCEP v1.2.0 includes PVS1 guidance with decision tree
- RNA splicing assay confirms aberrant splicing for c.1684+1G>A (PMID:30890586)
- Variant is at a canonical ±1
- 2 position satisfying the generic ClinGen SVI PVS1 framework (PMC6185798)
Still missing
- The PALB2 PVS1 decision tree graphic/table is not available locally
- final PVS1 strength assignment should be confirmed against the official VCEP decision tree
- NMD prediction status of the resulting transcript should be confirmed from the RNA data
Sources
PM2 SupportingNM_024675.3:c.1684+1G>A is absent from gnomAD v2.1 and v4.1. Under the PALB2 VCEP v1.2.0, PM2 is applied at Supporting strength (not Moderate) when the variant frequency is ≤0.000333% (1/300,000) in gnomAD v4. The variant meets this threshold as it is completely absent from both gnomAD datasets. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (0 alleles)
- Absent from gnomAD v4.1 (0 alleles)
- Variant frequency ≤0.000333% threshold met (VCEP PM2_Supporting rule)
Sources
PM5 SupportingUnder the PALB2 VCEP v1.2.0, PM5_Supporting is applied to splice variants with premature termination codons upstream of p.Tyr1183 when PVS1_VS(RNA) is applied based on high-quality observed splicing impact and the variant is NMD-prone. NM_024675.3:c.1684+1G>A is a canonical +1 splice site variant in intron 4 that has been shown to cause aberrant splicing by RNA analysis (PMID:30890586). The resulting transcript is predicted to introduce a premature termination codon far upstream of the p.Tyr1183 boundary and is expected to be NMD-prone, satisfying the VCEP PM5_Supporting conditions. Details ▾Hide ▴
Evidence considered
- PALB2 VCEP PM5 rule: PTC upstream of p.Tyr1183
- c.1684+1G>A is in exon 4 intron boundary
- well upstream of codon 1183
- RNA-confirmed aberrant splicing (PMID:30890586) supports PVS1_VS(RNA)
- a prerequisite for PM5_Supporting
- Predicted NMD-prone transcript
Still missing
- Exact NMD boundary prediction should be confirmed from the RNA assay data
- PM5_Supporting is conditional on PVS1_VS(RNA) being assigned
- if PVS1 strength is downgraded
- PM5 applicability should be re-evaluated
Sources
Not met · 10 · evaluated, threshold not reached
PS4 The PALB2 VCEP v1.2.0 requires case-control data with p≤0.05 and OR≥3 (or lower 95% CI≥1.5) for PS4. No case-control study specific to NM_024675.3:c.1684+1G>A was identified. While the variant has been observed in affected individuals submitted to ClinVar, these observations lack matched control denominator data and do not constitute a formal case-control study. Proband counting (PS4_Moderate) is not permitted under this VCEP. Details ▾Hide ▴
Evidence considered
- ClinVar variation ID 482029 has submissions from clinical laboratories reporting this variant in affected individuals
- Exploratory search found no formal case-control study for this variant
Still missing
- No case-control study with odds ratio available for this specific variant
- Proband counting disallowed by VCEP
Sources
PP1 No co-segregation data in affected family members was identified for NM_024675.3:c.1684+1G>A. The PALB2 VCEP v1.2.0 requires quantitative co-segregation analysis (LOD scores or Bayes Factors) for autosomal dominant conditions, or affected relative counts for autosomal recessive conditions. Neither type of evidence was found in ClinVar submissions, publications, or the exploratory evidence search. Details ▾Hide ▴
Evidence considered
- Exploratory search and literature review found no family segregation data
- ClinVar submissions do not include reported co-segregation information
Still missing
- No family studies with co-segregation analysis for this variant
- No LOD scores or LR values available
Sources
PP3 The PALB2 VCEP v1.2.0 PP3 rule for splicing variants is: 'Predicted impact via splicing (SpliceAI ≥0.2) for intronic variants OUTSIDE of donor and acceptor 1,2 sites.' NM_024675.3:c.1684+1G>A is a +1 donor site variant, which is AT a donor 1,2 site, not outside it. Therefore PP3 does not apply per VCEP rules. Additionally, the VCEP notes that 'PP3 for splice predictions may not be applied in addition to PVS1' to avoid double-counting the same splice-effect evidence. While SpliceAI predicts a high-impact donor loss (max delta = 0.94), this evidence is already captured under PVS1. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score = 0.94 (donor loss = 0.94)
- Variant is at the +1 canonical donor site
- inside the 1
- 2 boundary excluded by VCEP PP3 rule
- VCEP prohibits stacking PP3 with PVS1 for the same splice evidence
Sources
BA1 Under the PALB2 VCEP v1.2.0, BA1 requires Grpmax Filtering AF >0.1% in gnomAD v4. NM_024675.3:c.1684+1G>A is absent from gnomAD v4.1 (0 alleles). The BA1 threshold is not met. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v4.1
- VCEP BA1 threshold: Grpmax FAF >0.1%
Sources
BS1 Under the PALB2 VCEP v1.2.0, BS1 requires Grpmax Filtering AF >0.01% in gnomAD v4. NM_024675.3:c.1684+1G>A is absent from gnomAD v4.1. The BS1 threshold is not met. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v4.1
- VCEP BS1 threshold: Grpmax FAF >0.01%
Sources
BS2 The PALB2 VCEP v1.2.0 applies BS2 in the context of Fanconi anemia (recessive condition) using a points-per-proband system. No observation of this variant in a healthy individual (without Fanconi anemia) in a biallelic or appropriate heterozygous context was identified. Without specific proband data satisfying the VCEP BS2 tables, this criterion cannot be met. Details ▾Hide ▴
Evidence considered
- No healthy adult proband data available for BS2 evaluation
Still missing
- No Fanconi anemia proband data to evaluate BS2 points
Sources
BS4 The PALB2 VCEP v1.2.0 applies BS4 based on quantitative co-segregation analysis showing lack of segregation (LOD ≤-1.28 for Strong, ≤-0.64 for Moderate, ≤-0.32 for Supporting). No evidence of non-segregation was identified for NM_024675.3:c.1684+1G>A. No family studies demonstrating absence of the variant in affected relatives were found. Details ▾Hide ▴
Evidence considered
- No non-segregation data identified
Still missing
- No family studies available to evaluate BS4
Sources
BP1 The PALB2 VCEP v1.2.0 BP1 criterion applies specifically to missense variants in PALB2, based on the low rate of functional missense variants. NM_024675.3:c.1684+1G>A is a canonical splice site variant, not a missense variant, and therefore BP1 does not apply. Details ▾Hide ▴
BP4 The PALB2 VCEP v1.2.0 BP4 rule for splicing variants requires 'No predicted impact via splicing (SpliceAI ≤0.1).' NM_024675.3:c.1684+1G>A has a SpliceAI max delta score of 0.94 (donor loss = 0.94), well above the 0.1 threshold. BP4 is not met. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.94
- VCEP BP4 threshold: SpliceAI ≤0.1
Sources
BP7 The PALB2 VCEP v1.2.0 BP7 (in silico) is limited to synonymous and deep intronic variants beyond +7 (donor) and -21 (acceptor). NM_024675.3:c.1684+1G>A is at the +1 donor position, which is within the excluded canonical splice region. BP7(RNA) would require observed lack of aberrant splicing; however, RNA analysis in PMID:30890586 demonstrated that c.1684+1G>A does cause aberrant splicing. Therefore neither BP7 nor BP7(RNA) is met. Details ▾Hide ▴
Evidence considered
- Variant at +1 donor position
- inside the canonical splice region excluded from BP7
- RNA evidence (PMID:30890586) shows aberrant splicing
- contradicting BP7(RNA)
Sources
Not assessed · 1 · no assessment recorded
PS1 The PALB2 VCEP v1.2.0 PS1 criterion for splicing variants requires use of the PALB2 PS1 Splicing table (referenced to PMID:37352859). This table was not available in the case materials. Without access to the PS1 Splicing table, it cannot be determined whether a different nucleotide change at c.1684+1 (e.g., c.1684+1G>T or c.1684+1G>C) has been classified as pathogenic, which would be required to apply PS1. Details ▾Hide ▴
Evidence considered
- VCEP PS1 guidance directs to the PALB2 PS1 Splicing table (PMID:37352859)
Still missing
- PALB2 PS1 Splicing table (PMID:37352859) not available for review
- No comparator nucleotide change at c.1684+1 identified in available evidence
Sources
Not applicable · 15· recorded as not applicable Show reasons ▾Hide reasons ▴
PS2 VCEPThe PALB2 VCEP v1.2.0 specifies that PS2 is not applicable for autosomal dominant or autosomal recessive PALB2 conditions, as informative de novo occurrences have not been observed. Details ▾Hide ▴
Sources
PS3 VCEPThe PALB2 VCEP v1.2.0 specifies that PS3 (protein-level functional studies) is not applicable. For RNA-level evidence of splice defects, the VCEP directs use of PVS1_Strength(RNA) or BP7(RNA) codes instead. Details ▾Hide ▴
Sources
PM1 VCEPThe PALB2 VCEP v1.2.0 specifies that PM1 is not applicable because missense pathogenic variation in PALB2 is not yet confirmed as a mechanism of disease. Details ▾Hide ▴
Sources
PM3 N/ASkipped per workflow instruction. While PM3 is applicable under the PALB2 VCEP for Fanconi anemia (biallelic context), no evidence of this variant in trans with another PALB2 pathogenic variant in a Fanconi anemia patient was identified in available materials. Details ▾Hide ▴
Sources
PM4 VCEPThe PALB2 VCEP v1.2.0 specifies PM4 is not applicable. It is only used for stop-loss variants under this framework, and c.1684+1G>A is a canonical splice site substitution, not a stop-loss variant. Details ▾Hide ▴
Sources
PM6 VCEPThe PALB2 VCEP v1.2.0 specifies that PM6 is not applicable for autosomal dominant or autosomal recessive PALB2 conditions, as informative de novo occurrences have not been observed and de novo AR conditions are unlikely to be informed by phase. Details ▾Hide ▴
Sources
PP2 VCEPThe PALB2 VCEP v1.2.0 specifies that PP2 is not applicable because missense variation is not yet confirmed or refuted as a mechanism of disease for PALB2. Details ▾Hide ▴
Sources
PP4 VCEPThe PALB2 VCEP v1.2.0 specifies that PP4 is not applicable for autosomal dominant PALB2 conditions, as breast cancer is a disease with multiple genetic etiologies and there are no features that can readily distinguish hereditary from sporadic causes. Details ▾Hide ▴
Sources
PP5 VCEPThe PALB2 VCEP v1.2.0 designates PP5 as 'Not Applicable for this VCEP' as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. This criterion is not for use under the PALB2 VCEP framework. Details ▾Hide ▴
Sources
BS3 VCEPThe PALB2 VCEP v1.2.0 specifies that BS3 (protein-level functional studies showing no damaging effect) is not applicable. For RNA-level evidence of normal splicing, the VCEP directs use of BP7(RNA) instead. Details ▾Hide ▴
Sources
BP2 VCEPThe PALB2 VCEP v1.2.0 specifies that BP2 is not applicable; the ATM PM3/BP2 table should be used instead (ATM-specific). Details ▾Hide ▴
Sources
BP3 VCEPThe PALB2 VCEP v1.2.0 specifies BP3 is not applicable as small in-frame deletions/insertions are neither confirmed nor refuted as a mechanism of pathogenicity for PALB2, and PALB2 is not considered to have repetitive regions without known function. Details ▾Hide ▴
Sources
BP5 VCEPThe PALB2 VCEP v1.2.0 specifies that BP5 is not applicable. The VCEP notes that cases with multiple pathogenic variants have been observed with no noticeable difference in phenotype, and PALB2 has moderate penetrance with higher tolerance in the general population. Details ▾Hide ▴
Sources
BP6 VCEPThe PALB2 VCEP v1.2.0 designates BP6 as 'Not Applicable for this VCEP' as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Sources
PS5 N/AUnder the PALB2 VCEP framework, PP5 is explicitly designated 'Not Applicable for this VCEP' as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. PS5 in the generic ACMG/AMP framework serves a similar function and is not independently assessed under the VCEP. Details ▾Hide ▴
Sources
Identifiers
- Gene
- PALB2
- Transcript
- NM_024675.3
- Coding (HGVS c.)
- NM_024675.3:c.1684+1G>A
- Protein (HGVS p.)
- NP_078951.2:p.?
- GRCh38
- chr16:23634861 C>T
- GRCh37
- chr16:23646182 C>T
- ClinVar
- 482029
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
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
0 / 0 alleles
AF 0 · 0 homozygotes · FAF 0
By genetic ancestry
gnomAD-Canada
AF 0 · 0 / 0 alleles · 0 hom
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- 0.630
How the predictions were used
PP3 The PALB2 VCEP v1.2.0 PP3 rule for splicing variants is: 'Predicted impact via splicing (SpliceAI ≥0.2) for intronic variants OUTSIDE of donor and acceptor 1,2 sites.' NM_024675.3:c.1684+1G>A is a +1 donor site variant, which is AT a donor 1,2 site, not outside it. Therefore PP3 does not apply per VCEP rules. Additionally, the VCEP notes that 'PP3 for splice predictions may not be applied in addition to PVS1' to avoid double-counting the same splice-effect evidence. While SpliceAI predicts a high-impact donor loss (max delta = 0.94), this evidence is already captured under PVS1. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta score = 0.94 (donor loss = 0.94)
- Variant is at the +1 canonical donor site
- inside the 1
- 2 boundary excluded by VCEP PP3 rule
- VCEP prohibits stacking PP3 with PVS1 for the same splice evidence
Sources
BP4 The PALB2 VCEP v1.2.0 BP4 rule for splicing variants requires 'No predicted impact via splicing (SpliceAI ≤0.1).' NM_024675.3:c.1684+1G>A has a SpliceAI max delta score of 0.94 (donor loss = 0.94), well above the 0.1 threshold. BP4 is not met. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.94
- VCEP BP4 threshold: SpliceAI ≤0.1
Sources
BP7 The PALB2 VCEP v1.2.0 BP7 (in silico) is limited to synonymous and deep intronic variants beyond +7 (donor) and -21 (acceptor). NM_024675.3:c.1684+1G>A is at the +1 donor position, which is within the excluded canonical splice region. BP7(RNA) would require observed lack of aberrant splicing; however, RNA analysis in PMID:30890586 demonstrated that c.1684+1G>A does cause aberrant splicing. Therefore neither BP7 nor BP7(RNA) is met. Details ▾Hide ▴
Evidence considered
- Variant at +1 donor position
- inside the canonical splice region excluded from BP7
- RNA evidence (PMID:30890586) shows aberrant splicing
- contradicting BP7(RNA)
Sources
Statement
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.94). BayesDel score = 0.63.
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 16199547 ↗Splicing in action: assessing disease causing sequence changes.Baralle D et al. · 2005No paper-specific finding is recorded.
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PMID 17200671 ↗Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer.Reid S et al. · 2007No paper-specific finding is recorded.
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PMID 23334666 ↗The genetic landscape of high-risk neuroblastoma.Pugh TJ et al. · 2013No paper-specific finding is recorded.
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PMID 25099575 ↗Breast-cancer risk in families with mutations in PALB2.Antoniou AC et al. · 2014No paper-specific finding is recorded.
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PMID 28664506 ↗Prevalence and spectrum of germline rare variants in BRCA1/2 and PALB2 among breast cancer cases in Sarawak, Malaysia.Yang XR et al. · 2017No paper-specific finding is recorded.
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PMID 30890586 ↗Alternative splicing and ACMG-AMP-2015-based classification of PALB2 genetic variants: an ENIGMA report.Lopez-Perolio I et al. · 2019No 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.No paper-specific finding is recorded.
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PMID 17200668 ↗PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene.Rahman N et al. · 2007No 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
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.940
Open source ↗
ClinVar
2 Likely pathogenic · 1 Pathogenic
Open source ↗
COSMIC
Captured COSMIC 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/482029/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/16-23646182-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr16-23634861-C-T?dataset=gn…
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_024675.3%3Ac.1684…
- OncoKB ↗www.oncokb.org/gene/PALB2/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=PALB2+c.1684+1G%3EA
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
ClinVar
This variant has been reported in ClinVar as Likely pathogenic (2 clinical laboratories) and as Pathogenic (1 clinical laboratory) and as Uncertain Significance by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen (expert panel). (ClinVarID = 482029)
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.94). BayesDel score = 0.63.
Somatic
This variant has not previously been reported in somatic cancers (COSMIC).