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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000566341	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 17, 2023)	germline	clinical testing	Citation Link,
SCV000699542	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Apr 20, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000566341

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Sep 17, 2023)

germline

clinical testing

Citation Link,

SCV000699542

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Apr 20, 2017)

germline

clinical testing

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

LabCorp Variant Classification Summary - May 2015.docx

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

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

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

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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)."

#	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: May 7, 2024

ClinVar

Relating variation to medicine