U.S. flag

An official website of the United States government

NM_024675.4(PALB2):c.3096G>C (p.Met1032Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Aug 11, 2018
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:
RCV000217483.7

Allele description [Variation Report for NM_024675.4(PALB2):c.3096G>C (p.Met1032Ile)]

NM_024675.4(PALB2):c.3096G>C (p.Met1032Ile)

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.3096G>C (p.Met1032Ile)
HGVS:
  • NC_000016.10:g.23621379C>G
  • NG_007406.1:g.24979G>C
  • NM_024675.4:c.3096G>CMANE SELECT
  • NP_078951.2:p.Met1032Ile
  • NP_078951.2:p.Met1032Ile
  • LRG_308t1:c.3096G>C
  • LRG_308:g.24979G>C
  • LRG_308p1:p.Met1032Ile
  • NC_000016.9:g.23632700C>G
  • NM_024675.3:c.3096G>C
Protein change:
M1032I
Links:
dbSNP: rs778705498
NCBI 1000 Genomes Browser:
rs778705498
Molecular consequence:
  • NM_024675.4:c.3096G>C - 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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000276327Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Jun 18, 2015) 		germlineclinical testing

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

Citation Link,

SCV000686006Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Aug 11, 2018) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Breast cancer-associated missense mutants of the PALB2 WD40 domain, which directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair.

Park JY, Singh TR, Nassar N, Zhang F, Freund M, Hanenberg H, Meetei AR, Andreassen PR.

Oncogene. 2014 Oct 2;33(40):4803-12. doi: 10.1038/onc.2013.421. Epub 2013 Oct 21.

PubMed [citation]
PMID:
24141787
PMCID:
PMC3994186

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

Details of each submission

From Ambry Genetics, SCV000276327.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The p.M1032I variant (also known as c.3096G>C), located in coding exon 10 of the PALB2 gene, results from a G to C substitution at nucleotide position 3096. The methionine at codon 1032 is replaced by isoleucine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6497 samples (12994 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 70000 alleles tested) in our clinical cohort. This amino acid position is not well conserved on limited sequence alignment. 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 p.M1032I remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Color Diagnostics, LLC DBA Color Health, SCV000686006.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024