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NM_000321.3(RB1):c.1814+2T>G AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 29, 2015
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:
RCV000492308.2

Allele description [Variation Report for NM_000321.3(RB1):c.1814+2T>G]

NM_000321.3(RB1):c.1814+2T>G

Gene:
RB1:RB transcriptional corepressor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q14.2
Genomic location:
Preferred name:
NM_000321.3(RB1):c.1814+2T>G
HGVS:
  • NC_000013.11:g.48453113T>G
  • NG_009009.1:g.154367T>G
  • NM_000321.3:c.1814+2T>GMANE SELECT
  • NM_001407165.1:c.1814+2T>G
  • LRG_517t1:c.1814+2T>G
  • LRG_517:g.154367T>G
  • NC_000013.10:g.49027249T>G
  • NM_000321.2:c.1814+2T>G
Links:
dbSNP: rs1131690899
NCBI 1000 Genomes Browser:
rs1131690899
Molecular consequence:
  • NM_000321.3:c.1814+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407165.1:c.1814+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
Observations:
1

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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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000580854Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Pathogenic
(Dec 29, 2015) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Details of each submission

From Ambry Genetics, SCV000580854.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The c.1814+2T>G intronic variant results from a T to G substitution two nucleotides after coding exon 18 in the RB1 gene. 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 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.3% (greater than 600 alleles tested) in our clinical cohort. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice donor site are typically deleterious in nature (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). As such, the c.1814+2T>G variant is classified as a pathogenic mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Dec 24, 2023