NM_024675.4(PALB2):c.1058A>G (p.Lys353Arg) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 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:: RCV000774139.4

Allele description [Variation Report for NM_024675.4(PALB2):c.1058A>G (p.Lys353Arg)]

NM_024675.4(PALB2):c.1058A>G (p.Lys353Arg)

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.1058A>G (p.Lys353Arg)

HGVS:

NC_000016.10:g.23635488T>C
NG_007406.1:g.10870A>G
NM_024675.4:c.1058A>GMANE SELECT
NP_078951.2:p.Lys353Arg
NP_078951.2:p.Lys353Arg
LRG_308t1:c.1058A>G
LRG_308:g.10870A>G
LRG_308p1:p.Lys353Arg
NC_000016.9:g.23646809T>C
NM_024675.3:c.1058A>G

Protein change:

K353R

Links:

dbSNP: rs1567221700

NCBI 1000 Genomes Browser:

rs1567221700

Molecular consequence:

NM_024675.4:c.1058A>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

Recent activity

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MTMR4 [Apteryx mantelli]
MTMR4 [Apteryx mantelli]
Gene ID:106484674

Gene
ST6GALNAC2 [Hyaena hyaena]
ST6GALNAC2 [Hyaena hyaena]
Gene ID:120228158

Gene
dae04c12.y1 NICHD_XGC_Lu1 Xenopus laevis cDNA clone IMAGE:4632983 5' similar to ...
dae04c12.y1 NICHD_XGC_Lu1 Xenopus laevis cDNA clone IMAGE:4632983 5' similar to SW:RGS2_HUMAN P41220 REGULATOR OF G-PROTEIN SIGNALING 2, mRNA sequence
gi|13486018|gnl|dbEST|8226574|gb|BG 1.1|

Nucleotide
dae03c07.x1 NICHD_XGC_Lu1 Xenopus laevis cDNA clone IMAGE:4632972 3', mRNA seque...
dae03c07.x1 NICHD_XGC_Lu1 Xenopus laevis cDNA clone IMAGE:4632972 3', mRNA sequence
gi|13484507|gnl|dbEST|8225063|gb|BG 0.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000907839	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 4, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002715746	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 2, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000907839

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 4, 2018)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002715746

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 2, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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

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

Burden of hereditary cancer susceptibility in unselected patients with pancreatic ductal adenocarcinoma referred for germline screening.

Cremin C, Lee MK, Hong Q, Hoeschen C, Mackenzie A, Dixon K, McCullum M, Nuk J, Kalloger S, Karasinska J, Scudamore C, Kim PTW, Donnellan F, Lam ECS, Lim HJ, Neben CL, Stedden W, Zhou AY, Schaeffer DF, Sun S, Renouf DJ, Schrader KA.

Cancer Med. 2020 Jun;9(11):4004-4013. doi: 10.1002/cam4.2973. Epub 2020 Apr 7.

PubMed [citation]

PMID:: 32255556
PMCID:: PMC7286471

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000907839.1

#	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

From Ambry Genetics, SCV002715746.2

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

Description

The p.K353R variant (also known as c.1058A>G), located in coding exon 4 of the PALB2 gene, results from an A to G substitution at nucleotide position 1058. The lysine at codon 353 is replaced by arginine, an amino acid with highly similar properties. This variant was identified in 1/177 individuals with pancreatic ductal adenocarcinoma undergoing multi-gene panel testing (Cremin C et al. Cancer Med, 2020 06;9:4004-4013). 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

Last Updated: May 1, 2024

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