Genetic Information
Gene & Transcript Details
| ID | Status | Details |
|---|---|---|
| NM_024675.4 | MANE Select | 4008 nt | 154–3714 |
| NM_024675.3 | RefSeq Select | 4069 nt | 201–3761 |
Variant Details
Clinical & Population Data
Population Frequency
gnomADClinVar
OpenThis submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.
This variant is considered benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. This variant has been observed in trans with a known pathogenic variant in one or more individuals lacking clinical features consistent with gene-specific recessive disease.
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz.
"This variant has been reported in ClinVar as Uncertain significance (3 clinical laboratories) and as Likely benign (7 clinical laboratories) and as likely benign (1 clinical laboratories) and as Benign (2 clinical laboratories) and as Benign by ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen expert panel."
COSMIC Somatic Evidence
Open
Functional Impact & Domains
Functional Domain
Error in OpenAI Consolidation. OncoKB: PALB2E1083DPALB2E1083DSomaticNCBI Gene:79728|Show additional gene information Variant OverviewPALB2, a scaffolding protein involved in DNA repair, is altered in various cancers.The PALB2 E1083D mutation has not specifically been reviewed by the OncoKB team, and therefore its biological significance is unknown. JAX-CKB: PALB2 E1083D lies within WD repeat 5 of the Palb2 protein (UniProt.org). E1083D does not demonstrate reduced homology-directed DNA repair activity compared to wild-type Palb2 in cultured cells lacking Tp53 (PMID: 31636395), but has not been fully biochemically characterized and therefore, its effect on Palb2 protein function is unknown.
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Computational Analysis
Pathogenicity Predictions
SpliceAISpliceAI Scores
Window: ±500bp| Effect Type | Score | Position |
|---|---|---|
| Acceptor Loss (AL) | 0.0 | -359 bp |
| Donor Loss (DL) | 0.0 | 5 bp |
| Acceptor Gain (AG) | 0.2 | 47 bp |
| Donor Gain (DG) | 0.12 | -101 bp |
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
PM2 (Unknown (Pre-LLM))
From pre-LLM assessment (LLM Failed)
BP4 (Unknown (Pre-LLM))
From pre-LLM assessment (LLM Failed)