Submissions for variant NM_024675.4(PALB2):c.2571G>A (p.Leu857=)

dbSNP: rs587780821

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000123339	SCV000166653	likely benign	Familial cancer of breast	2023-06-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000486288	SCV000565352	uncertain significance	not provided	2017-02-08	criteria provided, single submitter	clinical testing	This variant is denoted PALB2 c.2571G>A at the DNA level. This variant is silent at the coding level, preserving a Leucine at codon 857. It is not predicted to cause abnormal splicing. This variant has not, to our knowledge, been published in the literature as being pathogenic or benign. PALB2 c.2571G>A was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The nucleotide which is altered, a guanine (G) at base 2571, is conserved through mammals. Based on currently available information, it is unclear whether PALB2 c.2571G>A is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics	RCV000560973	SCV000666869	likely benign	Hereditary cancer-predisposing syndrome	2015-10-08	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.
Color Diagnostics, LLC DBA Color Health	RCV000560973	SCV000685958	likely benign	Hereditary cancer-predisposing syndrome	2021-01-12	criteria provided, single submitter	clinical testing
GenomeConnect - Invitae Patient Insights Network	RCV001535717	SCV001749805	not provided	Fanconi anemia complementation group N; Hereditary cancer-predisposing syndrome		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 12-10-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.