NM_024675.4(PALB2):c.491T>G (p.Phe164Cys) AND Familial cancer of breast

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 15, 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:: RCV003607782.1

Allele description

NM_024675.4(PALB2):c.491T>G (p.Phe164Cys)

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.491T>G (p.Phe164Cys)

HGVS:

NC_000016.10:g.23636055A>C
NG_007406.1:g.10303T>G
NM_001407296.1:c.431T>G
NM_001407297.1:c.491T>G
NM_001407298.1:c.491T>G
NM_001407299.1:c.491T>G
NM_001407300.1:c.491T>G
NM_001407301.1:c.491T>G
NM_001407302.1:c.491T>G
NM_001407304.1:c.-395T>G
NM_001407305.1:c.-395T>G
NM_001407306.1:c.-395T>G
NM_001407307.1:c.-395T>G
NM_001407308.1:c.-395T>G
NM_001407309.1:c.-395T>G
NM_001407310.1:c.-395T>G
NM_001407311.1:c.-395T>G
NM_001407312.1:c.-105+5055T>G
NM_001407313.1:c.-105+5055T>G
NM_001407314.1:c.48+5055T>G
NM_024675.4:c.491T>GMANE SELECT
NP_001394225.1:p.Phe144Cys
NP_001394226.1:p.Phe164Cys
NP_001394227.1:p.Phe164Cys
NP_001394228.1:p.Phe164Cys
NP_001394229.1:p.Phe164Cys
NP_001394230.1:p.Phe164Cys
NP_001394231.1:p.Phe164Cys
NP_078951.2:p.Phe164Cys
NP_078951.2:p.Phe164Cys
LRG_308t1:c.491T>G
LRG_308:g.10303T>G
LRG_308p1:p.Phe164Cys
NC_000016.9:g.23647376A>C
NM_024675.3:c.491T>G

Protein change:

F144C

Molecular consequence:

NM_001407304.1:c.-395T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001407305.1:c.-395T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001407306.1:c.-395T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001407307.1:c.-395T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001407308.1:c.-395T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001407309.1:c.-395T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001407310.1:c.-395T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001407311.1:c.-395T>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001407312.1:c.-105+5055T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001407313.1:c.-105+5055T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001407314.1:c.48+5055T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001407296.1:c.431T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407297.1:c.491T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407298.1:c.491T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407299.1:c.491T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407300.1:c.491T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407301.1:c.491T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407302.1:c.491T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024675.4:c.491T>G - 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

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
SCV004402946	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 15, 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

SCV004402946

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 15, 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 Invitae, SCV004402946.1

#	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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 164 of the PALB2 protein (p.Phe164Cys).

#	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 8, 2024

ClinVar

Relating variation to medicine