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NM_000546.5(TP53):c.376-2dupA AND Li-Fraumeni syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 28, 2017
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:
RCV000232667.2

Allele description

NM_000546.5(TP53):c.376-2dupA

Gene:
TP53:tumor protein p53 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
17p13.1
Genomic location:
Preferred name:
NM_000546.5(TP53):c.376-2dupA
HGVS:
  • NC_000017.11:g.7675238dupT
  • NM_000546.5:c.376-2dupA
  • LRG_321t1:c.376-2dupA
  • LRG_321t2:c.376-2dupA
  • LRG_321t3:c.376-2dupA
  • LRG_321t4:c.376-2dupA
  • LRG_321t5:c.-23dupA
  • LRG_321t6:c.-23dupA
  • LRG_321t7:c.-23dupA
  • LRG_321t8:c.259-2dupA
  • LRG_321:g.17313dupA
  • NC_000017.10:g.7578556dupT
  • NM_000546.4:c.376-2dupA
Links:
dbSNP: rs751253294
NCBI 1000 Genomes Browser:
rs751253294
Molecular consequence:
  • NM_000546.5:c.376-2dupA - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Li-Fraumeni syndrome (LFS)
Synonyms:
Sarcoma family syndrome of Li and Fraumeni
Identifiers:
MedGen: C0085390; OMIM: PS151623

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000285192Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jun 28, 2017)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000285192.2

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

Description

This sequence change inserts a nucleotide near the splice acceptor site in intron 4 of the TP53 mRNA. It does not directly change the encoded amino acid sequence of the TP53 protein, but it affects a nucleotide within the consensus splice site of the intron. While this variant is present in population databases (rs751253294), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a TP53-related disease. ClinVar contains an entry for this variant (Variation ID: 185593). Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a rare intronic change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.

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

Last Updated: Jul 21, 2018