NM_024675.4(PALB2):c.3507_3508del (p.His1170fs) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Oct 21, 2022
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:: RCV000133490.22

Allele description

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)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000188564	SNPedia	no assertion criteria provided	pathogenic	germline	not provided	PubMed (1) [See all records that cite this PMID]
SCV000322189	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Oct 21, 2022)	germline	clinical testing	Citation Link,
SCV001961581	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Sep 1, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000188564

SNPedia

no assertion criteria provided

pathogenic

germline

not provided

PubMed (1)
[See all records that cite this PMID]

SCV000322189

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Oct 21, 2022)

germline

clinical testing

Citation Link,

SCV001961581

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Sep 1, 2021)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Details of each submission

From SNPedia, SCV000188564.1

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

Description

Converted during submission to Pathogenic.

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

From GeneDx, SCV000322189.9

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

Description

Frameshift variant predicted to result in an extension of the protein, as the last 17 amino acids are replaced with 18 different amino acids, which disrupts a portion of the seventh WD repeat and the critical region required for interaction with RAD51, BRCA2, POLH, and POLH DNA synthesis stimulation (Oliver 2009, Buisson 2010, Buisson 2014); Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26283626, 28825143, 17200671, 26314360, 16793542, 19609323, 26315354, 24556621, 25225577, 25099575, 19423707, 19584259, 24998779, 29431189, 29752822, 32339256, 30982232, 28888541, 20871615, 24485656)

#	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 CeGaT Center for Human Genetics Tuebingen, SCV001961581.13

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

#	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		2	not provided	not provided	not provided

Last Updated: Mar 16, 2024

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