NM_024675.4(PALB2):c.229T>C (p.Cys77Arg) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Sep 16, 2022
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:: RCV000485885.6

Allele description [Variation Report for NM_024675.4(PALB2):c.229T>C (p.Cys77Arg)]

NM_024675.4(PALB2):c.229T>C (p.Cys77Arg)

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.229T>C (p.Cys77Arg)

HGVS:

NC_000016.10:g.23636317A>G
NG_007406.1:g.10041T>C
NM_024675.4:c.229T>CMANE SELECT
NP_078951.2:p.Cys77Arg
NP_078951.2:p.Cys77Arg
LRG_308t1:c.229T>C
LRG_308:g.10041T>C
LRG_308p1:p.Cys77Arg
NC_000016.9:g.23647638A>G
NM_024675.3:c.229T>C

Protein change:

C77R

Links:

dbSNP: rs760045493

NCBI 1000 Genomes Browser:

rs760045493

Molecular consequence:

NM_024675.4:c.229T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Cetrariella delisei voucher LA31849 RNA polymerase II largest subunit (RPB2) gene, partial cds
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000567255	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (May 12, 2021)	germline	clinical testing	Citation Link,
SCV001192951	Leiden Open Variation Database	no assertion criteria provided	Uncertain significance (Oct 10, 2018)	germline	curation	PubMed (1) [See all records that cite this PMID]
SCV004222293	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Sep 16, 2022)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30287823, 33384714, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000567255

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(May 12, 2021)

germline

clinical testing

Citation Link,

SCV001192951

Leiden Open Variation Database

no assertion criteria provided

Uncertain significance
(Oct 10, 2018)

germline

curation

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

SCV004222293

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Sep 16, 2022)

unknown

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Citations

PubMed

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.

Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, Katagiri T, Yoshida T, Nakamura S, Sugano K, Miki Y, Hirata M, Matsuda K, Spurdle AB, Kubo M.

Nat Commun. 2018 Oct 4;9(1):4083. doi: 10.1038/s41467-018-06581-8.

PubMed [citation]

PMID:: 30287823
PMCID:: PMC6172276

Case Report: The Role of Molecular Analysis of the MUTYH Gene in Asymptomatic Individuals.

Fabišíková K, Hamidová O, Behulová RL, Závodná K, Priščáková P, Repiská V.

Front Genet. 2020;11:590486. doi: 10.3389/fgene.2020.590486.

PubMed [citation]

PMID:: 33384714
PMCID:: PMC7770176

See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV000567255.7

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

Description

In silico analysis supports that this missense variant does not alter protein structure/function; Co-observed with an apparently homozygous pathogenic MUTYH variant in an individual with colorectal and endometrial cancer (Fabikov 2020); This variant is associated with the following publications: (PMID: 30287823, 33384714)

#	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 Leiden Open Variation Database, SCV001192951.1

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

Description

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

#	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, SCV004222293.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The frequency of this variant in the general population, 0.0002 (7/34602 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported as an incidental finding in an individual with history of colorectal cancer and endometrial cancer who was found to carry a homozygous pathogenic MUTYH variant (33384714 (2020)), and has also been reported in unaffected control individuals (PMID: 30287823 (2018)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

#	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: Sep 8, 2024

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