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NM_024675.4(PALB2):c.1056_1057del (p.Lys353fs) AND Lynch syndrome 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 31, 2024
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:
RCV003485539.1

Allele description [Variation Report for NM_024675.4(PALB2):c.1056_1057del (p.Lys353fs)]

NM_024675.4(PALB2):c.1056_1057del (p.Lys353fs)

Gene:
PALB2:partner and localizer of BRCA2 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
16p12.2
Genomic location:
Preferred name:
NM_024675.4(PALB2):c.1056_1057del (p.Lys353fs)
Other names:
NM_024675.3:c.1056_1057del
HGVS:
  • NC_000016.10:g.23635490CT[1]
  • NG_007406.1:g.10866GA[1]
  • NM_024675.4:c.1056_1057delMANE SELECT
  • NP_078951.2:p.Lys353fs
  • LRG_308:g.10866GA[1]
  • NC_000016.9:g.23646810_23646811del
  • NC_000016.9:g.23646811CT[1]
  • NM_024675.3:c.1056_1057delGA
  • NM_024675.4:c.1056_1057delGAMANE SELECT
  • p.E352EFS*8
Protein change:
K353fs
Links:
dbSNP: rs180177099
NCBI 1000 Genomes Browser:
rs180177099
Molecular consequence:
  • NM_024675.4:c.1056_1057del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

Name:
Lynch syndrome 1
Synonyms:
COLON CANCER, FAMILIAL NONPOLYPOSIS, TYPE 1; MSH2-Related Hereditary Non-Polyposis Colon Cancer; Lynch syndrome I; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007356; MedGen: C2936783; Orphanet: 144; OMIM: 120435

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004239122KCCC/NGS Laboratory, Kuwait Cancer Control Center
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jan 31, 2024) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

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 KCCC/NGS Laboratory, Kuwait Cancer Control Center, SCV004239122.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedclinical testing PubMed (1)

Description

This sequence change creates a premature translational stop signal (p.Lys353Ilefs*7) in the PALB2 gene. It is expected to result in an absent or disrupted protein product. Loss of function variants in PALB2 are known to be pathogenic (PMID: 17200668, 17200671, 17200672, 24136930, 25099575). This variant is present in population databases (rs180177099, gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 18302019, 19763884). ClinVar contains an entry for this variant (Variation ID: 126587). For these reasons, this variant has been classified as Pathogenic. PALB2 (Partner and Localizer of BRCA2) germline pathogenic variants are associated with substantially increased breast cancer risk and smaller increased risk for pancreatic and ovarian cancer. Germline pathogenic variants in PALB2 are inherited in an autosomal dominant manner. The majority of individuals with a PALB2 pathogenic variant have inherited it from a parent. However, because of incomplete penetrance, variable age of cancer development, cancer risk reduction resulting from prophylactic surgery, or early death, not all individuals with a PALB2 pathogenic variant have a parent affected with cancer.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024