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NM_024675.4(PALB2):c.1696C>T (p.Arg566Cys) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Sep 17, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000586825.5

Allele description [Variation Report for NM_024675.4(PALB2):c.1696C>T (p.Arg566Cys)]

NM_024675.4(PALB2):c.1696C>T (p.Arg566Cys)

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.1696C>T (p.Arg566Cys)
HGVS:
  • NC_000016.10:g.23630458G>A
  • NG_007406.1:g.15900C>T
  • NM_024675.4:c.1696C>TMANE SELECT
  • NP_078951.2:p.Arg566Cys
  • NP_078951.2:p.Arg566Cys
  • LRG_308t1:c.1696C>T
  • LRG_308:g.15900C>T
  • LRG_308p1:p.Arg566Cys
  • NC_000016.9:g.23641779G>A
  • NM_024675.3:c.1696C>T
Protein change:
R566C
Links:
dbSNP: rs746582620
NCBI 1000 Genomes Browser:
rs746582620
Molecular consequence:
  • NM_024675.4:c.1696C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000566341GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Uncertain significance
(Sep 17, 2023)
germlineclinical testing

Citation Link,

SCV000699542Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Uncertain significance
(Apr 20, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.

Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S.

Gastroenterology. 2015 Sep;149(3):604-13.e20. doi: 10.1053/j.gastro.2015.05.006. Epub 2015 May 14.

PubMed [citation]
PMID:
25980754
PMCID:
PMC4550537

Details of each submission

From GeneDx, SCV000566341.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33471991, 35610400, 34326862, 25980754)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699542.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Variant summary: The PALB2 c.1696C>T (p.Arg566Cys) variant involves the alteration of a non-conserved nucleotide and 2/4 in silico tools (SNPsandGO not captured due to low reliability index) predict a benign outcome, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 1/95648, which does not exceed the estimated maximal expected allele frequency of a pathogenic PALB2 variant (0.0001563). A publication cites the variant in an affected individual, although with limited information (ie, lack of cosegregation data). A clinical diagnostic laboratory cites the variant with a classification of "uncertain significance." Therefore, until additional information becomes available (ie, clinical and functional data), the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)."

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024