NM_024675.4(PALB2):c.1547G>T (p.Arg516Ile) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 29, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002838870.3

Allele description [Variation Report for NM_024675.4(PALB2):c.1547G>T (p.Arg516Ile)]

NM_024675.4(PALB2):c.1547G>T (p.Arg516Ile)

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.1547G>T (p.Arg516Ile)

HGVS:

NC_000016.10:g.23634999C>A
NG_007406.1:g.11359G>T
NM_001407296.1:c.1487G>T
NM_001407297.1:c.1547G>T
NM_001407298.1:c.1547G>T
NM_001407299.1:c.1547G>T
NM_001407300.1:c.1547G>T
NM_001407301.1:c.1547G>T
NM_001407302.1:c.1547G>T
NM_001407304.1:c.662G>T
NM_001407305.1:c.662G>T
NM_001407306.1:c.662G>T
NM_001407307.1:c.662G>T
NM_001407308.1:c.662G>T
NM_001407309.1:c.662G>T
NM_001407310.1:c.662G>T
NM_001407311.1:c.662G>T
NM_024675.4:c.1547G>TMANE SELECT
NP_001394225.1:p.Arg496Ile
NP_001394226.1:p.Arg516Ile
NP_001394227.1:p.Arg516Ile
NP_001394228.1:p.Arg516Ile
NP_001394229.1:p.Arg516Ile
NP_001394230.1:p.Arg516Ile
NP_001394231.1:p.Arg516Ile
NP_001394233.1:p.Arg221Ile
NP_001394234.1:p.Arg221Ile
NP_001394235.1:p.Arg221Ile
NP_001394236.1:p.Arg221Ile
NP_001394237.1:p.Arg221Ile
NP_001394238.1:p.Arg221Ile
NP_001394239.1:p.Arg221Ile
NP_001394240.1:p.Arg221Ile
NP_078951.2:p.Arg516Ile
NP_078951.2:p.Arg516Ile
LRG_308t1:c.1547G>T
LRG_308:g.11359G>T
LRG_308p1:p.Arg516Ile
NC_000016.9:g.23646320C>A
NM_024675.3:c.1547G>T

Protein change:

R221I

Molecular consequence:

NM_001407296.1:c.1487G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407297.1:c.1547G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407298.1:c.1547G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407299.1:c.1547G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407300.1:c.1547G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407301.1:c.1547G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407302.1:c.1547G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407304.1:c.662G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407305.1:c.662G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407306.1:c.662G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407307.1:c.662G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407308.1:c.662G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407309.1:c.662G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407310.1:c.662G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001407311.1:c.662G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_024675.4:c.1547G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial; Hereditary breast cancer
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
SCV003214944	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 29, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003214944

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 29, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003214944.2

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 516 of the PALB2 protein (p.Arg516Ile).

#	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: Sep 29, 2024

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