NM_024675.4(PALB2):c.400G>A (p.Asp134Asn) AND Familial cancer of breast

Germline classification:: Conflicting interpretations of pathogenicity (5 submissions)
Last evaluated:: Feb 1, 2024
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:: RCV000114637.29

Allele description [Variation Report for NM_024675.4(PALB2):c.400G>A (p.Asp134Asn)]

NM_024675.4(PALB2):c.400G>A (p.Asp134Asn)

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.400G>A (p.Asp134Asn)

Other names:

p.D134N:GAC>AAC; NP_078951.2:p.Asp134Asn

HGVS:

NC_000016.10:g.23636146C>T
NG_007406.1:g.10212G>A
NM_024675.4:c.400G>AMANE SELECT
NP_078951.2:p.Asp134Asn
NP_078951.2:p.Asp134Asn
LRG_308t1:c.400G>A
LRG_308:g.10212G>A
LRG_308p1:p.Asp134Asn
NC_000016.9:g.23647467C>T
NM_024675.3:c.400G>A
p.D134N

Protein change:

D134N

Links:

dbSNP: rs139555085

NCBI 1000 Genomes Browser:

rs139555085

Molecular consequence:

NM_024675.4:c.400G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000153884	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Feb 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000267985	Cancer Genetics Laboratory, Peter MacCallum Cancer Centre	criteria provided, single submitter (Thompson et al. (Breast Cancer Res. 2015))	Uncertain significance (Jun 1, 2015)	germline	case-control	PubMed (1) [See all records that cite this PMID]
SCV000489425	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Likely benign (Oct 3, 2016)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23555315, 21932393, 25980754, 26283626 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV001192975	Leiden Open Variation Database	no assertion criteria provided	Likely benign (May 13, 2019)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 21932393, 25186627
SCV004019619	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Benign (Mar 31, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	1	not provided	not provided	1998	not provided	case-control
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	curation
not provided	unknown	unknown	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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Genome-wide testing of putative functional exonic variants in relationship with breast and prostate cancer risk in a multiethnic population.

Haiman CA, Han Y, Feng Y, Xia L, Hsu C, Sheng X, Pooler LC, Patel Y, Kolonel LN, Carter E, Park K, Le Marchand L, Van Den Berg D, Henderson BE, Stram DO.

PLoS Genet. 2013 Mar;9(3):e1003419. doi: 10.1371/journal.pgen.1003419. Epub 2013 Mar 28.

PubMed [citation]

PMID:: 23555315
PMCID:: PMC3610631

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV000153884.14

#	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 Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, SCV000267985.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	1998	not provided	not provided		1	not provided	not provided	not provided

From Counsyl, SCV000489425.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

#	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 Leiden Open Variation Database, SCV001192975.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)

Description

Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Marc Tischkowitz.

#	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 Myriad Genetics, Inc., SCV004019619.1

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

Description

This variant is considered benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. This variant has been observed in trans with a known pathogenic variant in one or more individuals lacking clinical features consistent with gene-specific recessive disease.

#	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: Jun 2, 2024

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