NM_024675.4(PALB2):c.1537A>G (p.Thr513Ala) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 18, 2023
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:: RCV000587874.5

Allele description [Variation Report for NM_024675.4(PALB2):c.1537A>G (p.Thr513Ala)]

NM_024675.4(PALB2):c.1537A>G (p.Thr513Ala)

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.1537A>G (p.Thr513Ala)

HGVS:

NC_000016.10:g.23635009T>C
NG_007406.1:g.11349A>G
NM_024675.4:c.1537A>GMANE SELECT
NP_078951.2:p.Thr513Ala
NP_078951.2:p.Thr513Ala
LRG_308t1:c.1537A>G
LRG_308:g.11349A>G
LRG_308p1:p.Thr513Ala
NC_000016.9:g.23646330T>C
NM_024675.3:c.1537A>G

Protein change:

T513A

Links:

dbSNP: rs1060502741

NCBI 1000 Genomes Browser:

rs1060502741

Molecular consequence:

NM_024675.4:c.1537A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Mus musculus protein phosphatase 1J (Ppm1j), mRNA
Mus musculus protein phosphatase 1J (Ppm1j), mRNA
gi|114205423|ref|NM_027982.2|

Nucleotide
Xenopus laevis MGC80207 protein, mRNA (cDNA clone MGC:80207 IMAGE:4970919), comp...
Xenopus laevis MGC80207 protein, mRNA (cDNA clone MGC:80207 IMAGE:4970919), complete cds
gi|49119134|gb|BC072839.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000699537	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (May 3, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV002004175	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 18, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000699537

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(May 3, 2016)

germline

clinical testing

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

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV002004175

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Sep 18, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000699537.1

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

Description

Variant summary: The c.1537A>G variant affects a non-conserved nucleotide, resulting in amino acid change from Thr to Ala. 3/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). This variant is found in 1/128274 control chromosomes at a frequency of 0.0000078, which does not exceed estimated maximal expected frequency of a pathogenic allele (0.0001563). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.

#	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 GeneDx, SCV002004175.3

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

Description

Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individual(s) with colorectal cancer (DeRycke et al., 2017); This variant is associated with the following publications: (PMID: 28944238, 26315354)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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