Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_024675.4(PALB2):c.2484C>T(p.Cys828Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
PALB2 (HGNC:26144): (partner and localizer of BRCA2) This gene encodes a protein that may function in tumor suppression. This protein binds to and colocalizes with the breast cancer 2 early onset protein (BRCA2) in nuclear foci and likely permits the stable intranuclear localization and accumulation of BRCA2. [provided by RefSeq, Jul 2008]
PALB2 Gene-Disease associations (from GenCC):
hereditary breast carcinoma
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
Our verdict: Benign. The variant received -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 16-23629670-G-A is Benign according to our data. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-23629670-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 225864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.137 with no splicing effect.
Cancer Genetics Laboratory, Peter MacCallum Cancer Centre
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:case-control
- -
Nov 15, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Jan 16, 2025
Myriad Genetics, Inc.
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
Hereditary cancer-predisposing syndromeBenign:2
Jan 22, 2024
Color Diagnostics, LLC DBA Color Health
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Sep 28, 2017
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method: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. -
not specifiedBenign:1
Oct 10, 2018
Leiden Open Variation Database
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:curation
Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa. -