NM_024675.4(PALB2):c.1001A>G (p.Tyr334Cys) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Jul 12, 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:: RCV000212784.18

Allele description [Variation Report for NM_024675.4(PALB2):c.1001A>G (p.Tyr334Cys)]

NM_024675.4(PALB2):c.1001A>G (p.Tyr334Cys)

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.1001A>G (p.Tyr334Cys)

Other names:

p.Y334C:TAC>TGC

HGVS:

NC_000016.10:g.23635545T>C
NG_007406.1:g.10813A>G
NM_024675.4:c.1001A>GMANE SELECT
NP_078951.2:p.Tyr334Cys
NP_078951.2:p.Tyr334Cys
LRG_308t1:c.1001A>G
LRG_308:g.10813A>G
LRG_308p1:p.Tyr334Cys
NC_000016.9:g.23646866T>C
NM_024675.3:c.1001A>G
Q86YC2:p.Tyr334Cys
p.Y334C

Protein change:

Y334C

Links:

UniProtKB: Q86YC2#VAR_066363; dbSNP: rs200620434

NCBI 1000 Genomes Browser:

rs200620434

Molecular consequence:

NM_024675.4:c.1001A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000149969	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jul 12, 2024)	germline	clinical testing	Citation Link,
SCV000889566	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely benign (Aug 2, 2023)	unknown	clinical testing	PubMed (15) [See all records that cite these PMIDs] 30374176, 26483394, 28767289, 28779002, 27516001, 22692731, 21618343, 20852946, 22241545, 24556926, 25186627, 26315354, 33471991, 33134171, 26467025
SCV002037053	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV002037250	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing

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

Outcomes of 92 patient-driven family studies for reclassification of variants of uncertain significance.

Tsai GJ, Rañola JMO, Smith C, Garrett LT, Bergquist T, Casadei S, Bowen DJ, Shirts BH.

Genet Med. 2019 Jun;21(6):1435-1442. doi: 10.1038/s41436-018-0335-7. Epub 2018 Oct 30.

PubMed [citation]

PMID:: 30374176

Prevalence of Pathogenic Mutations in Cancer Predisposition Genes among Pancreatic Cancer Patients.

Hu C, Hart SN, Bamlet WR, Moore RM, Nandakumar K, Eckloff BW, Lee YK, Petersen GM, McWilliams RR, Couch FJ.

Cancer Epidemiol Biomarkers Prev. 2016 Jan;25(1):207-11. doi: 10.1158/1055-9965.EPI-15-0455. Epub 2015 Oct 19.

PubMed [citation]

PMID:: 26483394
PMCID:: PMC4754121

See all PubMed Citations (15)

Details of each submission

From GeneDx, SCV000149969.19

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

Description

Observed in individuals with a personal or family history including breast, ovarian, and pancreatic cancers, as well as healthy individuals (PMID: 20852946, 21618343, 22692731, 24556926, 22241545, 26315354, 25186627, 26483394, 28779002, 28767289, 30374176, 32659497, 33471991, 29522266); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27363283, 28767289, 22692731, 21618343, 22241545, 25186627, 26483394, 20852946, 24556926, 26315354, 27150160, 28779002, 32659497, 30374176, 29300386, 33134171, 33471991, 29522266, 27516001, 35534704)

#	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, SCV000889566.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (15)

#	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 Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus, SCV002037053.1

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

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV002037250.1

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

Last Updated: Oct 26, 2024

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