NM_024675.4(PALB2):c.3507_3508del (p.His1170fs) AND PALB2-related disorder

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 5, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV004545747.2

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]

Observations:

Condition(s)

Name:: PALB2-related disorder
Synonyms:: PALB2-related condition; PALB2-Related Disorders
Identifiers:

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
SCV002107149	DASA	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 5, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 26283626, 25099575, 24556621, 26786923, 25225577, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002107149

DASA

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 5, 2022)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	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

Breast-cancer risk in families with mutations in PALB2.

Antoniou AC, Casadei S, Heikkinen T, Barrowdale D, Pylkäs K, Roberts J, Lee A, Subramanian D, De Leeneer K, Fostira F, Tomiak E, Neuhausen SL, Teo ZL, Khan S, Aittomäki K, Moilanen JS, Turnbull C, Seal S, Mannermaa A, Kallioniemi A, Lindeman GJ, Buys SS, et al.

N Engl J Med. 2014 Aug 7;371(6):497-506. doi: 10.1056/NEJMoa1400382.

PubMed [citation]

PMID:: 25099575
PMCID:: PMC4157599

See all PubMed Citations (6)

Details of each submission

From DASA, SCV002107149.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (6)

Description

The c.3507_3508del ;p.(His1170Phefs*?) is a null frameshift variant (NMD) in the PALB2 gene and predicts alteration of the nonsense-mediate decay - NMD is present in a relevant exon to the transcript - PVS1_moderate. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 140978; 25225577; PMID: 26283626; PMID: 25099575; PMID: 24556621; PMID: 26786923)PS4. The variant is present at low allele frequencies population databases (rs587776428 – gnomAD 0.00006579%; ABraOM no frequency - http://abraom.ib.usp.br.) - PM2_supporting. The variant co-segregated with disease in multiple affected family members (PMID: 25225577, 24556621) - PP1_moderate. In summary, the currently available evidence indicates that the variant is likely pathogenic.

#	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		1	not provided	not provided	not provided

Last Updated: Jul 29, 2024

ClinVar

Relating variation to medicine