NM_024675.4(PALB2):c.3235G>T (p.Ala1079Ser) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 27, 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:: RCV001797644.3

Allele description [Variation Report for NM_024675.4(PALB2):c.3235G>T (p.Ala1079Ser)]

NM_024675.4(PALB2):c.3235G>T (p.Ala1079Ser)

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.3235G>T (p.Ala1079Ser)

Other names:

p.A1079S:GCC>TCC; p.Ala1079Ser

HGVS:

NC_000016.10:g.23607979C>A
NG_007406.1:g.38379G>T
NM_024675.4:c.3235G>TMANE SELECT
NP_078951.2:p.Ala1079Ser
NP_078951.2:p.Ala1079Ser
LRG_308t1:c.3235G>T
LRG_308:g.38379G>T
LRG_308p1:p.Ala1079Ser
NC_000016.9:g.23619300C>A
NM_024675.3:c.3235G>T

Protein change:

A1079S

Links:

dbSNP: rs730881878

NCBI 1000 Genomes Browser:

rs730881878

Molecular consequence:

NM_024675.4:c.3235G>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Uncertain function

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002041774	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Mar 27, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26564480, 33471991, 34382369 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002041774

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Mar 27, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Mutation analysis of PALB2 gene in French breast cancer families.

Damiola F, Schultz I, Barjhoux L, Sornin V, Dondon MG, Eon-Marchais S, Marcou M; GENESIS Study Investigators., Caron O, Gauthier-Villars M, de Pauw A, Luporsi E, Berthet P, Delnatte C, Bonadona V, Maugard C, Pujol P, Lasset C, Longy M, Bignon YJ, Fricker JP, Andrieu N, et al.

Breast Cancer Res Treat. 2015 Dec;154(3):463-71. doi: 10.1007/s10549-015-3625-7. Epub 2015 Nov 12.

PubMed [citation]

PMID:: 26564480

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

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002041774.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: PALB2 c.3235G>T (p.Ala1079Ser) results in a conservative amino acid change located in the Partner and localiser of BRCA2, WD40 domain (IPR031920) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251472 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3235G>T has been reported in the literature in individuals affected with Breast Cancer (e.g. Damiola_2015, Dorling_2021) and acute myelogenous leukaemia (Beer_2021) without evidence for causality, and also in unaffected controls (Dorling_2021). These reports do not provide unequivocal conclusions about association of the variant with Breast Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submitters have assessed the variant since 2014: all six classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as 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: May 1, 2024

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