NM_024675.4(PALB2):c.2506G>A (p.Val836Ile) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Dec 29, 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:: RCV000586837.9

Allele description [Variation Report for NM_024675.4(PALB2):c.2506G>A (p.Val836Ile)]

NM_024675.4(PALB2):c.2506G>A (p.Val836Ile)

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.2506G>A (p.Val836Ile)

HGVS:

NC_000016.10:g.23629648C>T
NG_007406.1:g.16710G>A
NM_024675.4:c.2506G>AMANE SELECT
NP_078951.2:p.Val836Ile
NP_078951.2:p.Val836Ile
LRG_308t1:c.2506G>A
LRG_308:g.16710G>A
LRG_308p1:p.Val836Ile
NC_000016.9:g.23640969C>T
NM_024675.3:c.2506G>A

Protein change:

V836I

Links:

dbSNP: rs536644825

NCBI 1000 Genomes Browser:

rs536644825

Molecular consequence:

NM_024675.4:c.2506G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000568130	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Dec 29, 2022)	germline	clinical testing	Citation Link,
SCV000601762	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Jul 21, 2021)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 30635165, 28779002, 27093186, 26467025
SCV001193236	Leiden Open Variation Database	no assertion criteria provided	Uncertain significance (May 13, 2019)	germline	curation

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000568130

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Dec 29, 2022)

germline

clinical testing

Citation Link,

SCV000601762

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Jul 21, 2021)

unknown

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001193236

Leiden Open Variation Database

no assertion criteria provided

Uncertain significance
(May 13, 2019)

germline

curation

Help

Summary from all submissions

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

Citations

PubMed

A phase 1 study of veliparib, a PARP-1/2 inhibitor, with gemcitabine and radiotherapy in locally advanced pancreatic cancer.

Tuli R, Shiao SL, Nissen N, Tighiouart M, Kim S, Osipov A, Bryant M, Ristow L, Placencio-Hickok V, Hoffman D, Rokhsar S, Scher K, Klempner SJ, Noe P, Davis MJ, Wachsman A, Lo S, Jamil L, Sandler H, Piantadosi S, Hendifar A.

EBioMedicine. 2019 Feb;40:375-381. doi: 10.1016/j.ebiom.2018.12.060. Epub 2019 Jan 8.

PubMed [citation]

PMID:: 30635165
PMCID:: PMC6412162

Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.

Decker B, Allen J, Luccarini C, Pooley KA, Shah M, Bolla MK, Wang Q, Ahmed S, Baynes C, Conroy DM, Brown J, Luben R, Ostrander EA, Pharoah PD, Dunning AM, Easton DF.

J Med Genet. 2017 Nov;54(11):732-741. doi: 10.1136/jmedgenet-2017-104588. Epub 2017 Aug 4.

PubMed [citation]

PMID:: 28779002
PMCID:: PMC5740532

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV000568130.6

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30635165, 27093186, 28779002, 33128190, 24485656, 19609323, 30287823)

#	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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601762.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

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

From Leiden Open Variation Database, SCV001193236.1

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

Description

Curators: Marc Tischkowitz, Arleen D. Auerbach. Submitter to LOVD: Andreas Laner.

#	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: May 1, 2024

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