ClinVar Miner

Submissions for variant NM_024675.4(PALB2):c.2607C>T (p.Ser869=)

dbSNP: rs45542234
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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000123340 SCV000166656 benign Familial cancer of breast 2021-12-17 criteria provided, single submitter clinical testing
GeneDx RCV000212814 SCV000170857 benign not specified 2013-11-06 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 RCV000127296 SCV000213294 likely benign Hereditary cancer-predisposing syndrome 2014-06-20 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
PreventionGenetics,PreventionGenetics RCV000212814 SCV000314373 likely benign not specified criteria provided, single submitter clinical testing
Counsyl RCV000123340 SCV000488047 likely benign Familial cancer of breast 2015-12-16 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000127296 SCV000685963 benign Hereditary cancer-predisposing syndrome 2015-10-15 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587582 SCV000699571 benign not provided 2017-04-20 criteria provided, single submitter clinical testing Variant summary: The PALB2 c.2607C>T (p.Ser869Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. This variant was found in 68/121400 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.005766 (60/10406). This frequency is about 37 times the estimated maximal expected allele frequency of a pathogenic PALB2 variant (0.0001563), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. The variant has been reported in the literature, without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
PreventionGenetics,PreventionGenetics RCV000587582 SCV000807094 likely benign not provided 2014-03-26 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000212814 SCV002065061 likely benign not specified 2019-08-23 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000127296 SCV002530710 benign Hereditary cancer-predisposing syndrome 2020-12-03 criteria provided, single submitter curation
Leiden Open Variation Database RCV000212814 SCV001193263 benign not specified 2018-08-25 no assertion criteria provided curation Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000587582 SCV001553246 likely benign not provided no assertion criteria provided clinical testing The PALB2 p.Ser869= variant was identified in 1 of 1846 proband chromosomes (frequency: 0.0005) from individuals or families with breast cancer and was not identified in 2168 control chromosomes from healthy individuals (Rahman 2007). The variant was also identified in the following databases: dbSNP (ID: rs45542234) as "With Likely benign, other allele", ClinVar (2x benign, 3x likely benign), and Clinvitae. The variant was not identified in Cosmic, MutDB, LOVD 3.0, or the Zhejiang Colon Cancer Database. The variant was identified in control databases in 154 of 277240 chromosomes at a frequency of 0.0006 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 138 of 24036 chromosomes (freq: 0.006), Other in 3 of 6464 chromosomes (freq: 0.0005), Latino in 4 of 34420 chromosomes (freq: 0.0001), and South Asian in 9 of 30782 chromosomes (freq: 0.0003). The variant was not observed in the European, Ashkenazi Jewish, East Asian, or Finnish populations. The p.Ser869= 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. One of five in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000587582 SCV001977620 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000587582 SCV001977676 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000587582 SCV001979699 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000587582 SCV002034153 likely benign not provided no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV000212814 SCV002036891 benign not specified no assertion criteria provided clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000212814 SCV002551653 likely benign not specified 2021-12-30 no assertion criteria provided clinical testing

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