NM_024675.4(PALB2):c.1273G>A (p.Val425Met) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely benign (3 submissions)
Last evaluated:: Aug 25, 2021
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:: RCV000167189.12

Allele description [Variation Report for NM_024675.4(PALB2):c.1273G>A (p.Val425Met)]

NM_024675.4(PALB2):c.1273G>A (p.Val425Met)

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.1273G>A (p.Val425Met)

HGVS:

NC_000016.10:g.23635273C>T
NG_007406.1:g.11085G>A
NM_024675.4:c.1273G>AMANE SELECT
NP_078951.2:p.Val425Met
NP_078951.2:p.Val425Met
LRG_308t1:c.1273G>A
LRG_308:g.11085G>A
LRG_308p1:p.Val425Met
NC_000016.9:g.23646594C>T
NM_024675.3:c.1273G>A
Q86YC2:p.Val425Met
p.V425M

Protein change:

V425M

Links:

UniProtKB: Q86YC2#VAR_066366; dbSNP: rs576081828

NCBI 1000 Genomes Browser:

rs576081828

Molecular consequence:

NM_024675.4:c.1273G>A - 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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Gene ID:20521486

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unclassified Fungi internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene and internal transcribed spacer 2, complete sequence; and 28S ribosomal RNA gene, partial sequence.
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000218026	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Dec 2, 2020)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 18446436, 20722467, 21618343, 26489409, 28825143, 29387807 Citation Link,
SCV000685866	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Apr 7, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002530598	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely benign (Aug 25, 2021)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000218026

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Dec 2, 2020)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link,

SCV000685866

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Apr 7, 2020)

germline

clinical testing

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

SCV002530598

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Likely benign
(Aug 25, 2021)

germline

curation

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, curation

Citations

PubMed

The prevalence of PALB2 germline mutations in BRCA1/BRCA2 negative Chinese women with early onset breast cancer or affected relatives.

Cao AY, Huang J, Hu Z, Li WF, Ma ZL, Tang LL, Zhang B, Su FX, Zhou J, Di GH, Shen KW, Wu J, Lu JS, Luo JM, Yuan WT, Shen ZZ, Huang W, Shao ZM.

Breast Cancer Res Treat. 2009 Apr;114(3):457-62. doi: 10.1007/s10549-008-0036-z. Epub 2008 Apr 30.

PubMed [citation]

PMID:: 18446436

Evaluation of the contribution of the three breast cancer susceptibility genes CHEK2, STK11, and PALB2 in non-BRCA1/2 French Canadian families with high risk of breast cancer.

Guénard F, Pedneault CS, Ouellette G, Labrie Y, Simard J; INHERIT., Durocher F.

Genet Test Mol Biomarkers. 2010 Aug;14(4):515-26. doi: 10.1089/gtmb.2010.0027.

PubMed [citation]

PMID:: 20722467

See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV000218026.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000685866.3

#	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 Sema4, Sema4, SCV002530598.1

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

#	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: Oct 26, 2024

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