NM_024675.4(PALB2):c.2190C>G (p.Ile730Met) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 3, 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:: RCV003585692.1

Allele description [Variation Report for NM_024675.4(PALB2):c.2190C>G (p.Ile730Met)]

NM_024675.4(PALB2):c.2190C>G (p.Ile730Met)

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.2190C>G (p.Ile730Met)

HGVS:

NC_000016.10:g.23629964G>C
NG_007406.1:g.16394C>G
NM_001407296.1:c.2130C>G
NM_001407297.1:c.2190C>G
NM_001407298.1:c.2190C>G
NM_001407299.1:c.2190C>G
NM_001407300.1:c.2190C>G
NM_001407301.1:c.2190C>G
NM_001407302.1:c.2190C>G
NM_001407304.1:c.1305C>G
NM_001407305.1:c.1305C>G
NM_001407306.1:c.1305C>G
NM_001407307.1:c.1305C>G
NM_001407308.1:c.1305C>G
NM_001407309.1:c.1305C>G
NM_001407310.1:c.1305C>G
NM_001407311.1:c.1305C>G
NM_001407312.1:c.402C>G
NM_001407313.1:c.402C>G
NM_001407314.1:c.49-689C>G
NM_024675.4:c.2190C>GMANE SELECT
NP_001394225.1:p.Ile710Met
NP_001394226.1:p.Ile730Met
NP_001394227.1:p.Ile730Met
NP_001394228.1:p.Ile730Met
NP_001394229.1:p.Ile730Met
NP_001394230.1:p.Ile730Met
NP_001394231.1:p.Ile730Met
NP_001394233.1:p.Ile435Met
NP_001394234.1:p.Ile435Met
NP_001394235.1:p.Ile435Met
NP_001394236.1:p.Ile435Met
NP_001394237.1:p.Ile435Met
NP_001394238.1:p.Ile435Met
NP_001394239.1:p.Ile435Met
NP_001394240.1:p.Ile435Met
NP_001394241.1:p.Ile134Met
NP_001394242.1:p.Ile134Met
NP_078951.2:p.Ile730Met
NP_078951.2:p.Ile730Met
LRG_308t1:c.2190C>G
LRG_308:g.16394C>G
LRG_308p1:p.Ile730Met
NC_000016.9:g.23641285G>C
NM_024675.3:c.2190C>G

Protein change:

I134M

Molecular consequence:

NM_001407314.1:c.49-689C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001407296.1:c.2130C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407297.1:c.2190C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407298.1:c.2190C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407299.1:c.2190C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407300.1:c.2190C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407301.1:c.2190C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407302.1:c.2190C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407304.1:c.1305C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407305.1:c.1305C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407306.1:c.1305C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407307.1:c.1305C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407308.1:c.1305C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407309.1:c.1305C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407310.1:c.1305C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407311.1:c.1305C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407312.1:c.402C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001407313.1:c.402C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024675.4:c.2190C>G - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004357880	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 3, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33471991, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004357880

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 3, 2022)

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

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Breast Cancer Association Consortium., Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, Wahlström C, Pooley KA, Parsons MT, Fortuno C, Wang Q, Bolla MK, Dennis J, Keeman R, Alonso MR, Álvarez N, Herraez B, Fernandez V, Núñez-Torres R, Osorio A, Valcich J, Li M, et al.

N Engl J Med. 2021 Feb 4;384(5):428-439. doi: 10.1056/NEJMoa1913948. Epub 2021 Jan 20.

PubMed [citation]

PMID:: 33471991
PMCID:: PMC7611105

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV004357880.1

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

Description

This missense variant replaces isoleucine with methionine at codon 730 of the PALB2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been detected in a breast cancer case-control meta-analysis in 0/60466 cases and 1/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID PALB2_010926). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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: Feb 20, 2024

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