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NM_024675.4(PALB2):c.3116del (p.Asn1039fs)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
16
First in ClinVar:
Apr 4, 2013
Most recent Submission:
Jun 30, 2022
Last evaluated:
Feb 9, 2022
Accession:
VCV000126715.23
Variation ID:
126715
Description:
1bp deletion
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NM_024675.4(PALB2):c.3116del (p.Asn1039fs)

Allele ID
132225
Variant type
Deletion
Variant length
1 bp
Cytogenetic location
16p12.2
Genomic location
16: 23614089 (GRCh38) GRCh38 UCSC
16: 23625410 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NM_024675.4:c.3116del MANE Select NP_078951.2:p.Asn1039fs frameshift
NM_024675.3:c.3116delA
NC_000016.10:g.23614090del
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000016.10:23614088:TT:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA151245
OMIM: 610355.0005
OMIM: 610355.0009
dbSNP: rs180177133
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 4 criteria provided, multiple submitters, no conflicts Dec 8, 2021 RCV000114595.14
Pathogenic 5 criteria provided, multiple submitters, no conflicts Jan 30, 2022 RCV000131150.11
Pathogenic 3 criteria provided, multiple submitters, no conflicts Feb 9, 2022 RCV000235691.9
risk factor 1 no assertion criteria provided Feb 1, 2007 RCV000001309.3
Pathogenic 1 no assertion criteria provided Feb 1, 2007 RCV000114596.4
risk factor 1 no assertion criteria provided Apr 10, 2009 RCV000114597.6
Pathogenic 1 no assertion criteria provided - RCV001357097.2

Clinical features observed in individuals with this variant

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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
4348 4383

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter More information
Pathogenic
(Nov 20, 2015)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin: germline
University of Washington Department of Laboratory Medicine,University of Washington
Accession: SCV000266106.1
First in ClinVar: Mar 20, 2016
Last updated: Mar 20, 2016
Number of individuals with the variant: 1
Clinical Features:
stomach cancer (present)
Age: 30-39 years
Likely pathogenic
(Jun 01, 2015)
criteria provided, single submitter
Method: case-control
Familial cancer of breast
Cases recruited through familial  (more...)
Affected status: yes, no
Allele origin: germline
Cancer Genetics Laboratory,Peter MacCallum Cancer Centre
Accession: SCV000267972.1
First in ClinVar: May 11, 2016
Last updated: May 11, 2016
Publications:
PubMed (1)
PubMed: 26283626

Observation 1:

Number of individuals with the variant: 1
Zygosity: 1 Single Heterozygote
Sex: female
Geographic origin: Australia

Observation 2:

Number of individuals with the variant: 1
Zygosity: 1 Single Heterozygote
Sex: female
Geographic origin: Australia
Pathogenic
(Jun 21, 2016)
criteria provided, single submitter
Method: clinical testing
Familial cancer of breast
Affected status: unknown
Allele origin: unknown
Counsyl
Accession: SCV000488804.1
First in ClinVar: May 11, 2016
Last updated: May 11, 2016
Publications:
PubMed (2)
PubMed: 1720066826283626
Pathogenic
(Jan 26, 2018)
criteria provided, single submitter
Method: research
Hereditary cancer-predisposing syndrome
Affected status: yes
Allele origin: germline
Academic Department of Medical Genetics, University of Cambridge
Accession: SCV000992219.1
First in ClinVar: Sep 09, 2019
Last updated: Sep 09, 2019
Comment:
Identified as part of research study of individuals with multiple primary tumours referred for genetic assessment
Comment:
Application of AMCG guidelines 2015. Used other ClinVar submission evidence where relevant. Loss of heterozygosity in tumours or immunohistochemistry abnormalities considered functional evidence of pathogenicity.
Clinical Features:
Breast carcinoma (present) , Angiosarcoma (present) , Neoplasia of the nasopharynx (present)
Zygosity: 1 Single Heterozygote
Pathogenic
(Jan 22, 2020)
criteria provided, single submitter
Method: clinical testing
Familial cancer of breast
Affected status: no
Allele origin: germline
Division of Medical Genetics, University of Washington
Study: CSER_CHARM
Accession: SCV001434292.1
First in ClinVar: Oct 03, 2020
Last updated: Oct 03, 2020
Comment:
This variant leads to a translational frameshift and the introduction of a premature termination codon at position 2 of the new reading frame. The variant … (more)
Indication for testing: Family history of breast cancer
Pathogenic
(Oct 09, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin: germline
Ambry Genetics
Accession: SCV000186091.7
First in ClinVar: Aug 06, 2014
Last updated: Jun 22, 2020
Publications:
PubMed (7)
Comment:
The c.3116delA pathogenic mutation, located in coding exon 11 of the PALB2 gene, results from a deletion of one nucleotide at nucleotide position 3116, causing … (more)
Number of individuals with the variant: 1
Pathogenic
(Feb 11, 2021)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin: germline
Color Health, Inc
Accession: SCV000690900.3
First in ClinVar: Feb 19, 2018
Last updated: Jun 19, 2021
Comment:
This variant changes 1 nucleotide in exon 11 of the PALB2 gene, creating a premature translation stop signal. This variant is expected to result in … (more)
Pathogenic
(Aug 27, 2020)
criteria provided, single submitter
Method: clinical testing
not provided
Affected status: unknown
Allele origin: unknown
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001470039.2
First in ClinVar: Jan 26, 2021
Last updated: Jan 11, 2022
Publications:
PubMed (8)
Comment:
This frameshift variant causes the premature termination of PALB2 protein synthesis. In the published literature, it has been reported in individuals affected with breast cancer … (more)
Pathogenic
(Dec 08, 2021)
criteria provided, single submitter
Method: clinical testing
Familial cancer of breast
Affected status: unknown
Allele origin: germline
Invitae
Accession: SCV000260801.9
First in ClinVar: Jan 31, 2016
Last updated: Jun 18, 2022
Publications:
PubMed (10)
Comment:
This sequence change creates a premature translational stop signal (p.Asn1039Ilefs*2) in the PALB2 gene. It is expected to result in an absent or disrupted protein … (more)
Pathogenic
(Jan 30, 2022)
criteria provided, single submitter
Method: curation
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin: germline
Sema4,Sema4
Accession: SCV002530755.1
First in ClinVar: Jun 30, 2022
Last updated: Jun 30, 2022
Comment:
The PALB2 c.3116delA (p.N1039IfsX2) variant has been reported in heterozygosity in multiple individuals with pancreatic and breast cancer (PMID: 20412113, 17200668, among others). It has … (more)
Publications:
PubMed (4)
PubMed: 20412113172006683347199126283626
Pathogenic
(Feb 09, 2022)
criteria provided, single submitter
Method: clinical testing
Not Provided
Affected status: yes
Allele origin: germline
GeneDx
Accession: SCV000293156.11
First in ClinVar: Jul 24, 2016
Last updated: Jun 18, 2022
Comment:
Observed in individuals with PALB2-related cancers (Rahman 2007, Jones 2009, Slater 2010, Antoniou 2014, Thompson 2015); Frameshift variant predicted to result in protein truncation or … (more)
risk factor
(Feb 01, 2007)
no assertion criteria provided
Method: literature only
BREAST CANCER, SUSCEPTIBILITY TO
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000021459.1
First in ClinVar: Apr 04, 2013
Last updated: Apr 04, 2013
Publications:
PubMed (2)
PubMed: 1720067117200668
Comment on evidence:
In a North American family with Fanconi anemia, complementation group N (FANCN; 610832), Reid et al. (2007) found a 1-bp deletion, 3116delA (N1039fs), in exon … (more)
Pathogenic
(Feb 01, 2007)
no assertion criteria provided
Method: literature only
FANCONI ANEMIA, COMPLEMENTATION GROUP N
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000021458.1
First in ClinVar: Apr 04, 2013
Last updated: Apr 04, 2013
Publications:
PubMed (2)
PubMed: 1720067117200668
Comment on evidence:
In a North American family with Fanconi anemia, complementation group N (FANCN; 610832), Reid et al. (2007) found a 1-bp deletion, 3116delA (N1039fs), in exon … (more)
risk factor
(Apr 10, 2009)
no assertion criteria provided
Method: literature only
PANCREATIC CANCER, SUSCEPTIBILITY TO, 3
Affected status: not provided
Allele origin: germline
OMIM
Accession: SCV000021463.2
First in ClinVar: Apr 04, 2013
Last updated: Apr 22, 2019
Publications:
PubMed (1)
PubMed: 19264984
Comment on evidence:
In a patient with familial pancreatic cancer (PNCA3; 613348), Jones et al. (2009) identified a heterozygous germline deletion of adenine at nucleotide 3116 in exon … (more)
Pathogenic
(May 13, 2019)
no assertion criteria provided
Method: curation
not provided
Affected status: yes
Allele origin: germline
Leiden Open Variation Database
Accession: SCV001193357.1
First in ClinVar: Apr 06, 2020
Last updated: Apr 06, 2020
Publications:
PubMed (6)
Comment:
Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, LOVD-team, but with Curator vacancy, Marc Tischkowitz.
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
Malignant tumor of breast
Affected status: yes
Allele origin: unknown
Department of Pathology and Laboratory Medicine,Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001552448.1
First in ClinVar: Apr 13, 2021
Last updated: Apr 13, 2021
Comment:
The PALB2 p.Asn1039IlefsX2 variant was identified in 16 of 15604 proband chromosomes (frequency: 0.001) from individuals or families affected with Fanconi anemia, breast cancer, pancreatic … (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
Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. Breast Cancer Association Consortium. The New England journal of medicine 2021 PMID: 33471991
Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes. Whitworth J American journal of human genetics 2018 PMID: 29909963
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Improving performance of multigene panels for genomic analysis of cancer predisposition. Shirts BH Genetics in medicine : official journal of the American College of Medical Genetics 2016 PMID: 26845104
Prevalence of PALB2 mutations in Australian familial breast cancer cases and controls. Thompson ER Breast cancer research : BCR 2015 PMID: 26283626
Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. Couch FJ Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2015 PMID: 25452441
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
PALB2 mutations in European familial pancreatic cancer families. Slater EP Clinical genetics 2010 PMID: 20412113
Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Jones S Science (New York, N.Y.) 2009 PMID: 19264984
Analysis of FANCB and FANCN/PALB2 fanconi anemia genes in BRCA1/2-negative Spanish breast cancer families. García MJ Breast cancer research and treatment 2009 PMID: 18302019
Fanconi anemia is associated with a defect in the BRCA2 partner PALB2. Xia B Nature genetics 2007 PMID: 17200672
Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Reid S Nature genetics 2007 PMID: 17200671
PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Rahman N Nature genetics 2007 PMID: 17200668

Text-mined citations for rs180177133...

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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 Jun 30, 2022