NM_024675.4(PALB2):c.3054G>C (p.Glu1018Asp) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:: Dec 31, 2020
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:: RCV000130354.28

Allele description [Variation Report for NM_024675.4(PALB2):c.3054G>C (p.Glu1018Asp)]

NM_024675.4(PALB2):c.3054G>C (p.Glu1018Asp)

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.3054G>C (p.Glu1018Asp)

Other names:

p.E1018D:GAG>GAC; NM_024675.3(PALB2):c.3054G>C; p.Glu1018Asp

HGVS:

NC_000016.10:g.23621421C>G
NG_007406.1:g.24937G>C
NM_024675.4:c.3054G>CMANE SELECT
NP_078951.2:p.Glu1018Asp
NP_078951.2:p.Glu1018Asp
LRG_308t1:c.3054G>C
LRG_308:g.24937G>C
LRG_308p1:p.Glu1018Asp
NC_000016.9:g.23632742C>G
NM_024675.3:c.3054G>C
p.E1018D

Protein change:

E1018D

Links:

dbSNP: rs183489969

NCBI 1000 Genomes Browser:

rs183489969

Molecular consequence:

NM_024675.4:c.3054G>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000185205	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Jun 27, 2019)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 21285249, 22241545, 23977390, 25575445, 26283626, 26411315, 27616075, 27783279, 28580595, 31757951 Citation Link,
SCV000396077	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification 20161018)	Likely benign (Jun 14, 2016)	germline	clinical testing	ICSL_Variant_Classification_20161018.pdf, Citation Link,
SCV000822112	GeneKor MSA	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 1, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000902643	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Apr 19, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002530749	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely benign (Dec 31, 2020)	germline	curation	Citation Link

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

Citations

PubMed

Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer.

Casadei S, Norquist BM, Walsh T, Stray S, Mandell JB, Lee MK, Stamatoyannopoulos JA, King MC.

Cancer Res. 2011 Mar 15;71(6):2222-9. doi: 10.1158/0008-5472.CAN-10-3958. Epub 2011 Feb 1.

PubMed [citation]

PMID:: 21285249
PMCID:: PMC3059378

Rare germline mutations in PALB2 and breast cancer risk: a population-based study.

Tischkowitz M, Capanu M, Sabbaghian N, Li L, Liang X, Vallée MP, Tavtigian SV, Concannon P, Foulkes WD, Bernstein L; WECARE Study Collaborative Group., Bernstein JL, Begg CB.

Hum Mutat. 2012 Apr;33(4):674-80. doi: 10.1002/humu.22022. Epub 2012 Feb 15.

PubMed [citation]

PMID:: 22241545
PMCID:: PMC3767757

See all PubMed Citations (11)

Details of each submission

From Ambry Genetics, SCV000185205.10

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Illumina Laboratory Services, Illumina, SCV000396077.2

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

From GeneKor MSA, SCV000822112.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Color Diagnostics, LLC DBA Color Health, SCV000902643.1

#	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, SCV002530749.1

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

#	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: Nov 10, 2024

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