Submissions for variant NM_024675.4(PALB2):c.48+7G>C

gnomAD frequency: 0.00013  dbSNP: rs190626072

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000230746	SCV000290884	benign	Familial cancer of breast	2025-02-03	criteria provided, single submitter	clinical testing
Counsyl	RCV000230746	SCV000489493	likely benign	Familial cancer of breast	2016-10-11	criteria provided, single submitter	clinical testing
GeneDx	RCV000433452	SCV000521737	likely benign	not specified	2017-03-14	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.
Color Diagnostics, LLC DBA Color Health	RCV000580140	SCV000686061	likely benign	Hereditary cancer-predisposing syndrome	2015-09-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586925	SCV000699605	uncertain significance	not provided	2016-02-15	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000580140	SCV002531201	likely benign	Hereditary cancer-predisposing syndrome	2021-05-17	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000433452	SCV002551698	uncertain significance	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000230746	SCV004019134	benign	Familial cancer of breast	2023-03-30	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000586925	SCV001549182	likely benign	not provided		no assertion criteria provided	clinical testing	The PALB2 c.48+7G>C variant was not identified in the literature nor was it identified in the LOVD 3.0, Zhejiang Colon Cancer Database, databases. The variant was identified in dbSNP (ID: rs190626072) as With Likely benign allele, ClinVar (classified as likely benign by Invitae, Counsyl, GeneDx), databases. The variant was identified in control databases in 17 of 272618 chromosomes at a frequency of 0.000062 increasing the likelihood that this may be a low frequency benign variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017). The variant occurs outside of the splicing consensus sequence and 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume 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.
PreventionGenetics, part of Exact Sciences	RCV004541457	SCV004798156	likely benign	PALB2-related disorder	2022-02-21	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).