NM_000057.4(BLM):c.2250_2251insAAAT (p.Leu751fs) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Jul 17, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001014933.1

Allele description [Variation Report for NM_000057.4(BLM):c.2250_2251insAAAT (p.Leu751fs)]

NM_000057.4(BLM):c.2250_2251insAAAT (p.Leu751fs)

Gene:
BLM:BLM RecQ like helicase [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_000057.4(BLM):c.2250_2251insAAAT (p.Leu751fs)
HGVS:
  • NC_000015.10:g.90766966_90766967insAAAT
  • NG_007272.1:g.54595_54596insAAAT
  • NM_000057.4:c.2250_2251insAAATMANE SELECT
  • NM_001287246.2:c.2250_2251insAAAT
  • NM_001287247.2:c.2250_2251insAAAT
  • NM_001287248.2:c.1125_1126insAAAT
  • NP_000048.1:p.Leu751fs
  • NP_001274175.1:p.Leu751fs
  • NP_001274176.1:p.Leu751fs
  • NP_001274177.1:p.Leu376fs
  • LRG_20t1:c.2250_2251insAAAT
  • LRG_20:g.54595_54596insAAAT
  • NC_000015.9:g.91310196_91310197insAAAT
  • NM_000057.2:c.2250_2251insAAAT
  • NM_000057.3:c.2250_2251insAAAT
Protein change:
L376fs
Links:
dbSNP: rs786204471
NCBI 1000 Genomes Browser:
rs786204471
Molecular consequence:
  • NM_000057.4:c.2250_2251insAAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001287246.2:c.2250_2251insAAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001287247.2:c.2250_2251insAAAT - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001287248.2:c.1125_1126insAAAT - frameshift variant - [Sequence Ontology: SO:0001589]
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; MedGen: C0027672

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001175706Ambry Geneticscriteria provided, single submitter
Pathogenic
(Jul 17, 2019)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Syndrome-causing mutations of the BLM gene in persons in the Bloom's Syndrome Registry.

German J, Sanz MM, Ciocci S, Ye TZ, Ellis NA.

Hum Mutat. 2007 Aug;28(8):743-53.

PubMed [citation]
PMID:
17407155

Inherited DNA-Repair Defects in Colorectal Cancer.

AlDubayan SH, Giannakis M, Moore ND, Han GC, Reardon B, Hamada T, Mu XJ, Nishihara R, Qian Z, Liu L, Yurgelun MB, Syngal S, Garraway LA, Ogino S, Fuchs CS, Van Allen EM.

Am J Hum Genet. 2018 Mar 1;102(3):401-414. doi: 10.1016/j.ajhg.2018.01.018. Epub 2018 Feb 22.

PubMed [citation]
PMID:
29478780
PMCID:
PMC5985280

Details of each submission

From Ambry Genetics, SCV001175706.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The c.2250_2251insAAAT variant, located in coding exon 9 of the BLM gene, results from an insertion of 4 nucleotides at position 2250, causing a translational frameshift with a predicted alternate stop codon (p.L751Kfs*25). This alteration has been detected in the compound heterozygous state in two individuals affected with Bloom syndrome (German J et al. Hum. Mutat. 2007 Aug;28:743-53). This alteration has also been detected in a patient affected with colorectal cancer (AlDubayan SH et al. Am. J. Hum. Genet. 2018 03;102:401-414). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Jun 14, 2021

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