NM_024675.4(PALB2):c.1454C>T (p.Thr485Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 2, 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:: RCV000165637.13

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:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

Recent activity

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UMC-p4mm3-001-e08 4mm ovarian follicle p4mm Sus scrofa cDNA 3', mRNA sequence
UMC-p4mm3-001-e08 4mm ovarian follicle p4mm Sus scrofa cDNA 3', mRNA sequence
gi|51311013|gnl|dbEST|25052406|gb|C 54.1|

Nucleotide
Rattus norvegicus coiled-coil domain containing 51 (Ccdc51), mRNA; nuclear gene ...
Rattus norvegicus coiled-coil domain containing 51 (Ccdc51), mRNA; nuclear gene for mitochondrial product
gi|2007537952|ref|NM_001014098.2|

Nucleotide
PREDICTED: Rattus norvegicus coiled-coil domain containing 51 (Ccdc51), transcri...
PREDICTED: Rattus norvegicus coiled-coil domain containing 51 (Ccdc51), transcript variant X1, mRNA
gi|2678965301|ref|XM_006243789.5|

Nucleotide
zinc finger E-box-binding homeobox 2 isoform 1 [Homo sapiens]
zinc finger E-box-binding homeobox 2 isoform 1 [Homo sapiens]
gi|7662184|ref|NP_055610.1|

Protein
JGI_CAAP6080.fwd NIH_XGC_tropInt1 Xenopus tropicalis cDNA clone IMAGE:7712506 5'...
JGI_CAAP6080.fwd NIH_XGC_tropInt1 Xenopus tropicalis cDNA clone IMAGE:7712506 5', mRNA sequence
gi|58783419|gnl|dbEST|27676811|gb|C 92.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000216373	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 2, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26315354, 28135145 Citation Link,
SCV000685879	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 30, 2018)	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

SCV000216373

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 2, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000685879

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 30, 2018)

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

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 Ambry Genetics, SCV000216373.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.T485I variant (also known as c.1454C>T), located in coding exon 4 of the PALB2 gene, results from a C to T substitution at nucleotide position 1454. The threonine at codon 485 is replaced by isoleucine, an amino acid with similar properties. This variant has been reported in 1/1058 individuals diagnosed with colon cancer (Yurgelun MB et al. J. Clin. Oncol. 2017 Apr;35:1086-1095). In another study, this alteration was observed in 0/3236 cases with invasive epithelial ovarian cancer and 1/3431 controls (Ramus SJ et al. J. Natl. Cancer Inst., 2015 Nov;107:). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

From Color Diagnostics, LLC DBA Color Health, SCV000685879.3

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

#	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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