Submissions for variant NM_024675.4(PALB2):c.1572A>G (p.Ser524=)

gnomAD frequency: 0.00312  dbSNP: rs45472400

Total submissions: 27

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000114480	SCV000166645	benign	Familial cancer of breast	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000212796	SCV000170872	benign	not specified	2013-11-05	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000127311	SCV000212781	likely benign	Hereditary cancer-predisposing syndrome	2016-01-26	criteria provided, single submitter	clinical testing	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.
Cancer Genetics Laboratory, Peter MacCallum Cancer Centre	RCV000114480	SCV000268033	likely benign	Familial cancer of breast	2015-06-01	criteria provided, single submitter	case-control
Illumina Laboratory Services, Illumina	RCV000127311	SCV000396109	likely benign	Hereditary cancer-predisposing syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000261837	SCV000396110	likely benign	Fanconi anemia complementation group N	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV000488265	SCV000575047	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	PALB2: BP4, BP7, BS2
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000127311	SCV000576466	likely benign	Hereditary cancer-predisposing syndrome	2018-05-23	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000488265	SCV000604600	benign	not provided	2021-01-04	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000127311	SCV000685888	benign	Hereditary cancer-predisposing syndrome	2015-04-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000212796	SCV000807077	benign	not specified	2017-01-30	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000212796	SCV000889576	benign	not specified	2021-05-27	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798294	SCV002043585	benign	Breast and/or ovarian cancer	2023-04-12	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000212796	SCV002070053	likely benign	not specified	2021-12-30	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000127311	SCV002530624	benign	Hereditary cancer-predisposing syndrome	2020-07-02	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000212796	SCV002551676	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000488265	SCV005213525	likely benign	not provided		criteria provided, single submitter	not provided
True Health Diagnostics	RCV000127311	SCV000788085	likely benign	Hereditary cancer-predisposing syndrome	2018-01-12	no assertion criteria provided	clinical testing
Leiden Open Variation Database	RCV000488265	SCV001193121	benign	not provided	2019-05-13	no assertion criteria provided	curation	Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357887	SCV001553482	benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The PALB2 p.Ser524= variant was identified in 53 of 11538 proband chromosomes (frequency: 0.005) from Dutch, Spanish, German, Russian, American, British, Australian and Polish individuals or families with BRCA1/2 negative ovarian, pancreatic and female and male breast cancer with or without a family history of breast cancer and was identified in 48 of 7064 control chromosomes from healthy individuals (Adank 2011, Blanco 2012, Bogdanova 2011, Ding 2011, Garcia 2009, Hellebrand 2011, Hofstatter 2011, Kluska 2017, Rahman 2007, Teo 2013, Thompson 2015, Tischkowitz 2008). The variant was also identified in dbSNP (ID: rs45472400) “With other allele”, ClinVar (classified benign by Invitae, GeneDx, Quest Diagnostics, ARUP Laboratories, PALB2 database; and likely benign by Ambry Genetics, Illumina, Praxis fuer Humangenetik Tuebingen, Peter MacCallum cancer Centre and Institute for biomarker Research, Clinvitae (6x), Zhejiang Colon Cancer Database (2x), and was not identified in Cosmic. The variant was identified in control databases in 899 (2 homozygous) of 277242 chromosomes at a frequency of 0.003 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017). Breakdown of the observations by population include African in 22 of 24026 chromosomes (freq. 0.0009), other in 14 of 6468 chromosomes (freq. 0.002), Latino in 86 (1 homozygous) of 34420 chromosomes (freq. 0.002), European Non-Finnish in 621 (1 homozygous) of 126732 chromosomes (freq. 0.005), Ashkenazi Jewish in 2 of 10152 chromosomes (freq:0.0002), European Finnish in 44 of 25792 chromosomes (freq:0.002) and South Asian in 110 of 30782 chromosomes (freq. 0.004); it was not seen in the East Asian population. The p.Ser524= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000488265	SCV001742654	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000488265	SCV001808107	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000488265	SCV001905893	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000488265	SCV001931658	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000488265	SCV001957189	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000488265	SCV001966960	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000488265	SCV002036258	likely benign	not provided		no assertion criteria provided	clinical testing