NM_024675.4(PALB2):c.3426_3429del (p.Leu1142fs) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Jan 10, 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:: RCV000133486.6

Allele description [Variation Report for NM_024675.4(PALB2):c.3426_3429del (p.Leu1142fs)]

NM_024675.4(PALB2):c.3426_3429del (p.Leu1142fs)

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.3426_3429del (p.Leu1142fs)

HGVS:

NC_000016.10:g.23603591AAGT[1]
NG_007406.1:g.42760ACTT[1]
NM_024675.4:c.3426_3429delMANE SELECT
NP_078951.2:p.Leu1142fs
LRG_308:g.42760ACTT[1]
NC_000016.9:g.23614912AAGT[1]
NC_000016.9:g.23614912_23614915del
NC_000016.9:g.23614915_23614918del
NC_000016.9:g.23614915_23614918del
NC_000016.9:g.23614916_23614919del
NM_024675.3:c.3426_3429delACTT
p.L1142FFS*20
p.Leu1142Phefs*20

Protein change:

L1142fs

Links:

dbSNP: rs587776424

NCBI 1000 Genomes Browser:

rs587776424

Molecular consequence:

NM_024675.4:c.3426_3429del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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TBC1 domain family member 16 isoform X14 [Homo sapiens]
TBC1 domain family member 16 isoform X14 [Homo sapiens]
gi|2462553112|ref|XP_054171041.1|

Protein
PubChem Substance Links for Gene (Select 71489) (15)
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000188560	SNPedia	no assertion criteria provided	pathogenic	germline	not provided	PubMed (1) [See all records that cite this PMID]
SCV000568196	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jan 10, 2023)	germline	clinical testing	Citation Link,
SCV000601784	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jun 19, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25099575, 28319063, 26467025
SCV001193409	Leiden Open Variation Database	no assertion criteria provided	Pathogenic (Feb 28, 2020)	germline	curation	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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing, curation

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

Compromised BRCA1-PALB2 interaction is associated with breast cancer risk.

Foo TK, Tischkowitz M, Simhadri S, Boshari T, Zayed N, Burke KA, Berman SH, Blecua P, Riaz N, Huo Y, Ding YC, Neuhausen SL, Weigelt B, Reis-Filho JS, Foulkes WD, Xia B.

Oncogene. 2017 Jul 20;36(29):4161-4170. doi: 10.1038/onc.2017.46. Epub 2017 Mar 20.

PubMed [citation]

PMID:: 28319063
PMCID:: PMC5519427

See all PubMed Citations (4)

Details of each submission

From SNPedia, SCV000188560.1

#	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, SCV000568196.5

#	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 protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25099575, 30287823, 30128536, 34196900, 34399810, 29922827)

#	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 Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601784.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

#	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 Leiden Open Variation Database, SCV001193409.1

#	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: Yukihide Momozawa.

#	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

Last Updated: May 1, 2024

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