NM_024675.4(PALB2):c.1279G>C (p.Ala427Pro) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 30, 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:: RCV003053610.3

Allele description [Variation Report for NM_024675.4(PALB2):c.1279G>C (p.Ala427Pro)]

NM_024675.4(PALB2):c.1279G>C (p.Ala427Pro)

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.1279G>C (p.Ala427Pro)

HGVS:

NC_000016.10:g.23635267C>G
NG_007406.1:g.11091G>C
NM_001407296.1:c.1219G>C
NM_001407297.1:c.1279G>C
NM_001407298.1:c.1279G>C
NM_001407299.1:c.1279G>C
NM_001407300.1:c.1279G>C
NM_001407301.1:c.1279G>C
NM_001407302.1:c.1279G>C
NM_001407304.1:c.394G>C
NM_001407305.1:c.394G>C
NM_001407306.1:c.394G>C
NM_001407307.1:c.394G>C
NM_001407308.1:c.394G>C
NM_001407309.1:c.394G>C
NM_001407310.1:c.394G>C
NM_001407311.1:c.394G>C
NM_024675.4:c.1279G>CMANE SELECT
NP_001394225.1:p.Ala407Pro
NP_001394226.1:p.Ala427Pro
NP_001394227.1:p.Ala427Pro
NP_001394228.1:p.Ala427Pro
NP_001394229.1:p.Ala427Pro
NP_001394230.1:p.Ala427Pro
NP_001394231.1:p.Ala427Pro
NP_001394233.1:p.Ala132Pro
NP_001394234.1:p.Ala132Pro
NP_001394235.1:p.Ala132Pro
NP_001394236.1:p.Ala132Pro
NP_001394237.1:p.Ala132Pro
NP_001394238.1:p.Ala132Pro
NP_001394239.1:p.Ala132Pro
NP_001394240.1:p.Ala132Pro
NP_078951.2:p.Ala427Pro
NP_078951.2:p.Ala427Pro
LRG_308t1:c.1279G>C
LRG_308:g.11091G>C
LRG_308p1:p.Ala427Pro
NC_000016.9:g.23646588C>G
NM_024675.3:c.1279G>C

Protein change:

A132P

Molecular consequence:

NM_001407296.1:c.1219G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407297.1:c.1279G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407298.1:c.1279G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407299.1:c.1279G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407300.1:c.1279G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407301.1:c.1279G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407302.1:c.1279G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407304.1:c.394G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407305.1:c.394G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407306.1:c.394G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407307.1:c.394G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407308.1:c.394G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407309.1:c.394G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407310.1:c.394G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001407311.1:c.394G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_024675.4:c.1279G>C - 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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Mucopolysaccharidosis VII
Mucopolysaccharidosis VII
Mucopolysaccharidosis characterized by excessive dermatan and heparan sulfates in the urine and Hurler-like features. It is caused by a deficiency of beta-glucuronidase....<br/>Year introduced: 1992

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003334248	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 30, 2023)	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

SCV003334248

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 30, 2023)

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, SCV003334248.2

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 427 of the PALB2 protein (p.Ala427Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PALB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2118390). 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. 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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