NM_024675.4(PALB2):c.3088A>G (p.Thr1030Ala) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 14, 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:: RCV001306754.6

Allele description [Variation Report for NM_024675.4(PALB2):c.3088A>G (p.Thr1030Ala)]

NM_024675.4(PALB2):c.3088A>G (p.Thr1030Ala)

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.3088A>G (p.Thr1030Ala)

HGVS:

NC_000016.10:g.23621387T>C
NG_007406.1:g.24971A>G
NM_024675.4:c.3088A>GMANE SELECT
NP_078951.2:p.Thr1030Ala
LRG_308t1:c.3088A>G
LRG_308:g.24971A>G
NC_000016.9:g.23632708T>C
NM_024675.3:c.3088A>G

Protein change:

T1030A

Links:

dbSNP: rs1040452708

NCBI 1000 Genomes Browser:

rs1040452708

Molecular consequence:

NM_024675.4:c.3088A>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

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Homo sapiens SPATA8 antisense RNA 1 (head to head) (SPATA8-AS1), transcript vari...
Homo sapiens SPATA8 antisense RNA 1 (head to head) (SPATA8-AS1), transcript variant 2, long non-coding RNA
gi|491230408|ref|NR_102754.1|

Nucleotide
Rattus norvegicus DERP6 mRNA, complete cds
Rattus norvegicus DERP6 mRNA, complete cds
gi|48237487|gb|AY623900.1|

Nucleotide
Rai12 protein [Rattus norvegicus]
Rai12 protein [Rattus norvegicus]
gi|165970864|gb|AAI58570.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001496136	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 14, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26315354, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001496136

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 14, 2023)

germline

clinical testing

PubMed (2)
[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

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, SCV001496136.4

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

Description

This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1030 of the PALB2 protein (p.Thr1030Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with ovarian cancer (PMID: 26315354). ClinVar contains an entry for this variant (Variation ID: 830190). 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 expected to disrupt PALB2 protein function with a positive predictive value of 80%. 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: Sep 29, 2024

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