ClinVar Miner

Submissions for variant NM_024675.3(PALB2):c.400G>A (p.Asp134Asn) (rs139555085)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000128994 SCV000172888 benign Hereditary cancer-predisposing syndrome 2015-06-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene,Co-occurence with a mutation in another gene that clearly explains a proband's phenotype,Subpopulation frequency in support of benign classification,in silico models in agreement (benign)
Cancer Genetics Laboratory,Peter MacCallum Cancer Centre RCV000114637 SCV000267985 uncertain significance Familial cancer of breast 2015-06-01 criteria provided, single submitter case-control
Color RCV000128994 SCV000686056 likely benign Hereditary cancer-predisposing syndrome 2015-09-23 criteria provided, single submitter clinical testing
Counsyl RCV000114637 SCV000489425 likely benign Familial cancer of breast 2016-10-03 criteria provided, single submitter clinical testing
GeneDx RCV000200990 SCV000211544 likely benign not specified 2018-01-16 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.
Integrated Genetics/Laboratory Corporation of America RCV000590187 SCV000699604 benign not provided 2017-05-22 criteria provided, single submitter clinical testing Variant summary: The PALB2 c.400G>A (p.Asp134Asn) variant involves the alteration of a non-conserved nucleotide and 5/5 in silico tools predict a benign outcome. However, these predictions have yet to be functionally assessed. This variant was found in 54/125366 control chromosomes, predominantly observed in the African cohort at a frequency of 0.004997 (52/10406). This frequency is about 32 times the estimated maximal expected allele frequency of a pathogenic PALB2 variant (0.0001563). Therefore, suggesting this is likely a benign polymorphism found primarily in population(s) of African origin. Multiple publications have cited the variant in affected individuals, however, with limited information (ie, lack of co-occurrence and/or cosegregation data). An internal LCA sample reports the variant to co-occur with a pathogenic PMS2 variant, c.2186_2187delTC (p.Leu729fs - classified as pathogenic by LCA). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as "likely benign/benign." Taken together, this variant is classified as benign.
Invitae RCV000114637 SCV000153884 benign Familial cancer of breast 2018-01-09 criteria provided, single submitter clinical testing
PALB2 database RCV000114637 SCV000148584 likely pathogenic Familial cancer of breast 2012-07-16 no assertion criteria provided literature only
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000200990 SCV000601791 likely benign not specified 2017-03-30 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590187 SCV000888379 benign not provided 2018-04-20 criteria provided, single submitter clinical testing

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