NM_024675.4(PALB2):c.3507_3508del (p.His1170fs) AND Familial cancer of breast

Germline classification:: Pathogenic/Likely pathogenic (7 submissions)
Last evaluated:: Dec 8, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000211073.17

Allele description [Variation Report for NM_024675.4(PALB2):c.3507_3508del (p.His1170fs)]

NM_024675.4(PALB2):c.3507_3508del (p.His1170fs)

Gene:

PALB2:partner and localizer of BRCA2 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_024675.4(PALB2):c.3507_3508del (p.His1170fs)

Other names:

NP_078951.2:p.His1170PhefsTer19

HGVS:

NC_000016.10:g.23603513AG[1]
NG_007406.1:g.42843TC[1]
NM_024675.4:c.3507_3508delMANE SELECT
NP_078951.2:p.His1170fs
LRG_308:g.42843TC[1]
NC_000016.9:g.23614833_23614834del
NC_000016.9:g.23614834AG[1]
NM_024675.3:c.3507_3508delTC
NM_024675.4:c.3507_3508del
p.H1170Ffs*19

Protein change:

H1170fs

Links:

dbSNP: rs587776428

NCBI 1000 Genomes Browser:

rs587776428

Molecular consequence:

NM_024675.4:c.3507_3508del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000267975	Cancer Genetics Laboratory, Peter MacCallum Cancer Centre	criteria provided, single submitter (Thompson et al. (Breast Cancer Res. 2015))	Likely pathogenic (Jun 1, 2015)	germline	case-control	PubMed (1) [See all records that cite this PMID]
SCV000290879	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 8, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 24556621, 25099575, 25225577, 26283626, 26314354, 26786923, 17200671, 28492532
SCV000677794	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Likely pathogenic (May 18, 2017)	unknown	clinical testing	PubMed (8) [See all records that cite these PMIDs] 25099575, 25225577, 26315354, 19423707, 24556621, 24998779, 19584259, 26786923 Citation Link,
SCV001193423	Leiden Open Variation Database	no assertion criteria provided	Pathogenic (May 13, 2019)	germline	curation	PubMed (1) [See all records that cite this PMID]
SCV001251423	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 28, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004019688	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (Mar 31, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19423707, 19609323 Citation Link,
SCV004202784	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 6, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	1996	not provided	curation, case-control
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Prevalence of PALB2 mutations in Australian familial breast cancer cases and controls.

Thompson ER, Gorringe KL, Rowley SM, Wong-Brown MW, McInerny S, Li N, Trainer AH, Devereux L, Doyle MA, Li J, Lupat R, Delatycki MB; LifePool Investigators., Mitchell G, James PA, Scott RJ, Campbell IG.

Breast Cancer Res. 2015 Aug 19;17:111. doi: 10.1186/s13058-015-0627-7.

PubMed [citation]

PMID:: 26283626
PMCID:: PMC4539664

Ischemic preconditioning and thrombosis.

Kristensen SD, Ropcke DM.

Vasa. 2015 Jul;44(4):243-4. doi: 10.1024/0301-1526/a000437. No abstract available.

PubMed [citation]

PMID:: 26314354

See all PubMed Citations (14)

Details of each submission

From Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, SCV000267975.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	case-control	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1996	not provided	not provided		1	not provided	not provided	not provided

From Invitae, SCV000290879.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change results in a frameshift in the PALB2 gene (p.His1170Phefs*19). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 17 amino acid(s) of the PALB2 protein and extend the protein by 1 additional amino acid residues. This variant is present in population databases (rs587781411, gnomAD 0.1%). This frameshift has been observed in individual(s) with breast, ovarian and prostate cancer and breast cancer (PMID: 24556621, 25099575, 25225577, 26283626, 26314354, 26786923). It has also been observed to segregate with disease in related individuals. This variant is also known as c.3504_3505del. ClinVar contains an entry for this variant (Variation ID: 140978). This variant disrupts a region of the PALB2 protein in which other variant(s) (p.Y1183*) have been determined to be pathogenic (PMID: 17200671). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Counsyl, SCV000677794.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Leiden Open Variation Database, SCV001193423.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

Description

Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001251423.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Criteria applied: PVS1_MOD,PS4,PM2_SUP_MOD,PP1

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004019688.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is considered likely pathogenic. This variant creates a frameshift predicted to result in the incorporation of abnormal amino acid sequence into the protein product and abnormal protein elongation. Functional studies indicate this variant impacts protein function [PMID: 19423707, 19609323].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004202784.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 15, 2024

Relating variation to medicine