Submissions for variant NM_024675.4(PALB2):c.72del (p.Arg26fs)

dbSNP: rs180177142

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164203	SCV000214824	pathogenic	Hereditary cancer-predisposing syndrome	2023-03-20	criteria provided, single submitter	clinical testing	The c.72delG pathogenic mutation, located in coding exon 2 of the PALB2 gene, results from a deletion of one nucleotide at nucleotide position 72, causing a translational frameshift with a predicted alternate stop codon (p.R26Gfs*7). This alteration has been reported in a familial breast and pancreatic cancer kindred (Peterlongo P et al. Breast Cancer Res. Treat. 2011 Apr;126:825-8). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Invitae	RCV000114655	SCV000826868	pathogenic	Familial cancer of breast	2023-12-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg26Glyfs*7) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 21184274, 25099575). This variant is also known as Leu24fs. ClinVar contains an entry for this variant (Variation ID: 126766). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000164203	SCV001342842	pathogenic	Hereditary cancer-predisposing syndrome	2022-05-06	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 2 of the PALB2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in several individuals affected with breast cancer (PMID: 21184274, 25099575), including one proband with strong family history (PIMD: 21184274). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PALB2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000114655	SCV001934523	likely pathogenic	Familial cancer of breast	2020-09-15	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001030114	SCV002010953	pathogenic	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000114655	SCV004189361	pathogenic	Familial cancer of breast	2023-09-05	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
GeneDx	RCV001030114	SCV005080881	pathogenic	not provided	2023-12-06	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; This variant is associated with the following publications: (PMID: 21184274, 24556926, 37507557, 25099575, 30303537)
Leiden Open Variation Database	RCV001030114	SCV001192916	pathogenic	not provided	2019-05-13	no assertion criteria provided	curation	Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz.