NM_024675.4(PALB2):c.1454C>T (p.Thr485Ile) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 4, 2023
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:: RCV000205126.12

Allele description [Variation Report for NM_024675.4(PALB2):c.1454C>T (p.Thr485Ile)]

NM_024675.4(PALB2):c.1454C>T (p.Thr485Ile)

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.1454C>T (p.Thr485Ile)

HGVS:

NC_000016.10:g.23635092G>A
NG_007406.1:g.11266C>T
NM_024675.4:c.1454C>TMANE SELECT
NP_078951.2:p.Thr485Ile
NP_078951.2:p.Thr485Ile
LRG_308t1:c.1454C>T
LRG_308:g.11266C>T
LRG_308p1:p.Thr485Ile
NC_000016.9:g.23646413G>A
NM_024675.3:c.1454C>T
p.T485I

Protein change:

T485I

Links:

dbSNP: rs786202699

NCBI 1000 Genomes Browser:

rs786202699

Molecular consequence:

NM_024675.4:c.1454C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial
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
SCV000261195	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 4, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26315354, 28135145, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000261195

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 4, 2023)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer.

Ramus SJ, Song H, Dicks E, Tyrer JP, Rosenthal AN, Intermaggio MP, Fraser L, Gentry-Maharaj A, Hayward J, Philpott S, Anderson C, Edlund CK, Conti D, Harrington P, Barrowdale D, Bowtell DD, Alsop K, Mitchell G; AOCS Study Group., Cicek MS, Cunningham JM, Fridley BL, et al.

J Natl Cancer Inst. 2015 Aug 27;107(11). doi:pii: djv214. 10.1093/jnci/djv214. Print 2015 Nov.

PubMed [citation]

PMID:: 26315354
PMCID:: PMC4643629

Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, Ukaegbu CI, Brais LK, McNamara PG, Mayer RJ, Schrag D, Meyerhardt JA, Ng K, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Syngal S.

J Clin Oncol. 2017 Apr 1;35(10):1086-1095. doi: 10.1200/JCO.2016.71.0012. Epub 2017 Jan 30.

PubMed [citation]

PMID:: 28135145
PMCID:: PMC5455355

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000261195.10

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

Description

This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 485 of the PALB2 protein (p.Thr485Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with colorectal cancer (PMID: 26315354, 28135145). ClinVar contains an entry for this variant (Variation ID: 186107). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PALB2 protein function. 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.

#	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 1, 2024

ClinVar

Relating variation to medicine