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NM_024675.3(PALB2):c.2515-1G>C

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely pathogenic(3);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
4 (Most recent: Jan 7, 2021)
Last evaluated:
Sep 2, 2020
Accession:
VCV000216006.7
Variation ID:
216006
Description:
single nucleotide variant
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NM_024675.3(PALB2):c.2515-1G>C

Allele ID
213165
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
16p12.2
Genomic location
16: 23629276 (GRCh38) GRCh38 UCSC
16: 23640597 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000016.10:g.23629276C>G
NC_000016.9:g.23640597C>G
NM_024675.3:c.2515-1G>C splice acceptor
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000016.10:23629275:C:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00000
Exome Aggregation Consortium (ExAC) 0.00001
Links
ClinGen: CA337588
dbSNP: rs587776417
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Likely pathogenic 1 criteria provided, single submitter Sep 2, 2020 RCV000198016.3
Likely pathogenic 1 criteria provided, single submitter Apr 1, 2019 RCV000985889.1
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations May 7, 2019 RCV000580827.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
PALB2 - - GRCh38
GRCh37
3869 3902

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Aug 11, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000685956.2
Submitted: (Nov 06, 2018)
Evidence details
Likely pathogenic
(Apr 01, 2019)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001134545.1
Submitted: (Oct 16, 2019)
Evidence details
Comment:
The variant disrupts a canonical splice site, and is therefore predicted to result in the loss of a functional protein. Variant identified at frequency that … (more)
Uncertain significance
(May 07, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV001176611.2
Submitted: (Nov 30, 2020)
Evidence details
Comment:
The c.2515-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 6 of the PALB2 gene. This nucleotide position … (more)
Likely pathogenic
(Sep 02, 2020)
criteria provided, single submitter
Method: clinical testing
Familial cancer of breast
Allele origin: germline
Invitae
Accession: SCV000253717.4
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (7)
Comment:
This sequence change affects an acceptor splice site in intron 5 of the PALB2 gene. It is expected to disrupt RNA splicing and likely results … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Alternative splicing and ACMG-AMP-2015-based classification of PALB2 genetic variants: an ENIGMA report. Lopez-Perolio I Journal of medical genetics 2019 PMID: 30890586
Breast-cancer risk in families with mutations in PALB2. Antoniou AC The New England journal of medicine 2014 PMID: 25099575
The PALB2 gene is a strong candidate for clinical testing in BRCA1- and BRCA2-negative hereditary breast cancer. Janatova M Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 2013 PMID: 24136930
Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Casadei S Cancer research 2011 PMID: 21285249
Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Jones S Science (New York, N.Y.) 2009 PMID: 19264984
PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Rahman N Nature genetics 2007 PMID: 17200668
Splicing in action: assessing disease causing sequence changes. Baralle D Journal of medical genetics 2005 PMID: 16199547

Text-mined citations for rs587776417...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 10, 2021