NM_024675.4(PALB2):c.3428T>A (p.Leu1143His) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Feb 13, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000116104.19

Allele description [Variation Report for NM_024675.4(PALB2):c.3428T>A (p.Leu1143His)]

NM_024675.4(PALB2):c.3428T>A (p.Leu1143His)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_024675.4(PALB2):c.3428T>A (p.Leu1143His)

Other names:

p.L1143H:CTT>CAT

HGVS:

NC_000016.10:g.23603592A>T
NG_007406.1:g.42766T>A
NM_024675.4:c.3428T>AMANE SELECT
NP_078951.2:p.Leu1143His
NP_078951.2:p.Leu1143His
LRG_308t1:c.3428T>A
LRG_308:g.42766T>A
LRG_308p1:p.Leu1143His
NC_000016.9:g.23614913A>T
NM_024675.3:c.3428T>A
p.L1143H

Protein change:

L1143H

Links:

dbSNP: rs62625284

NCBI 1000 Genomes Browser:

rs62625284

Molecular consequence:

NM_024675.4:c.3428T>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000186860	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Likely benign (Dec 18, 2018)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 20852946, 22692731, 24556926, 25186627, 25479140, 26283626, 26315354, 26564480 Citation Link,
SCV000838993	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (Jul 2, 2018)	unknown	clinical testing	Citation Link,
SCV000902660	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (May 6, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002531178	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Feb 13, 2022)	germline	curation	PubMed (17) [See all records that cite these PMIDs] 31512090, 22692731, 20852946, 27878467, 25479140, 33471991, 33558524, 33980423, 31451522, 26315354, 24556926, 32658311, 31206626, 25186627, 29522266, 28944238, 31757951 Citation Link

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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	germline	unknown	1	not provided	not provided	1	not provided	clinical testing, curation

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

Mutation analysis of PALB2 gene in French breast cancer families.

Damiola F, Schultz I, Barjhoux L, Sornin V, Dondon MG, Eon-Marchais S, Marcou M; GENESIS Study Investigators., Caron O, Gauthier-Villars M, de Pauw A, Luporsi E, Berthet P, Delnatte C, Bonadona V, Maugard C, Pujol P, Lasset C, Longy M, Bignon YJ, Fricker JP, Andrieu N, et al.

Breast Cancer Res Treat. 2015 Dec;154(3):463-71. doi: 10.1007/s10549-015-3625-7. Epub 2015 Nov 12.

PubMed [citation]

PMID:: 26564480

See all PubMed Citations (20)

Details of each submission

From Ambry Genetics, SCV000186860.7

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

Description

This alteration is classified as likely benign based on a combination of the following: 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.

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

From Mendelics, SCV000838993.2

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

From Color Diagnostics, LLC DBA Color Health, SCV000902660.1

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Sema4, Sema4, SCV002531178.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (17)

#	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

Last Updated: Mar 10, 2024

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