NM_024675.4(PALB2):c.2509G>A (p.Glu837Lys) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 24, 2023
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:: RCV000656936.11

Allele description [Variation Report for NM_024675.4(PALB2):c.2509G>A (p.Glu837Lys)]

NM_024675.4(PALB2):c.2509G>A (p.Glu837Lys)

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.2509G>A (p.Glu837Lys)

Other names:

p.E837K:GAA>AAA

HGVS:

NC_000016.10:g.23629645C>T
NG_007406.1:g.16713G>A
NM_024675.4:c.2509G>AMANE SELECT
NP_078951.2:p.Glu837Lys
NP_078951.2:p.Glu837Lys
LRG_308t1:c.2509G>A
LRG_308:g.16713G>A
LRG_308p1:p.Glu837Lys
NC_000016.9:g.23640966C>T
NM_024675.3:c.2509G>A
p.E837K

Protein change:

E837K

Links:

dbSNP: rs587778587

NCBI 1000 Genomes Browser:

rs587778587

Molecular consequence:

NM_024675.4:c.2509G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Hirundinidae sequence.
Hirundinidae sequence.
PopSet: 440505301

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000149996	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Feb 27, 2020)	germline	clinical testing	Citation Link,
SCV002046129	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jan 24, 2023)	unknown	clinical testing	PubMed (10) [See all records that cite these PMIDs] 30287823, 32019277, 33309985, 28380452, 33471991, 29190888, 28796317, 27783279, 26411315, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000149996

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(Feb 27, 2020)

germline

clinical testing

Citation Link,

SCV002046129

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jan 24, 2023)

unknown

clinical testing

PubMed (10)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.

Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, Katagiri T, Yoshida T, Nakamura S, Sugano K, Miki Y, Hirata M, Matsuda K, Spurdle AB, Kubo M.

Nat Commun. 2018 Oct 4;9(1):4083. doi: 10.1038/s41467-018-06581-8.

PubMed [citation]

PMID:: 30287823
PMCID:: PMC6172276

Detection of Germline Mutations in Breast Cancer Patients with Clinical Features of Hereditary Cancer Syndrome Using a Multi-Gene Panel Test.

Shin HC, Lee HB, Yoo TK, Lee ES, Kim RN, Park B, Yoon KA, Park C, Lee ES, Moon HG, Noh DY, Kong SY, Han W.

Cancer Res Treat. 2020 Jul;52(3):697-713. doi: 10.4143/crt.2019.559. Epub 2020 Feb 4.

PubMed [citation]

PMID:: 32019277
PMCID:: PMC7373875

See all PubMed Citations (10)

Details of each submission

From GeneDx, SCV000149996.16

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

Description

This variant is associated with the following publications: (PMID: 26411315, 29190888, 24728327, 24755471, 27783279, 24163242, 28796317, 29338689)

#	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, SCV002046129.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

The frequency of this variant in the general population, 0.0042 (16/3818 chromosomes in the Korean subpopulation, http://gnomad.broadinstitute.org), is higher than would generally be expected for pathogenic variants in this gene. In the published literature, the variant has been reported in individuals affected with hereditary breast and/or ovarian cancer (PMIDs: 32019277 (2020), 30287823 (2018)) and colorectal cancer (PMIID: 33309985 (2020)). It has also been reported in a breast cancer association study where the variant was found in individuals with breast cancer as well as in unaffected controls (PMIDs: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/PALB2)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

#	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: Nov 3, 2024

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