NM_000057.4(BLM):c.2407dup (p.Trp803fs) AND Bloom syndrome

Clinical significance:Pathogenic (Last evaluated: Oct 28, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000035004.6

Allele description [Variation Report for NM_000057.4(BLM):c.2407dup (p.Trp803fs)]

NM_000057.4(BLM):c.2407dup (p.Trp803fs)

Gene:
BLM:BLM RecQ like helicase [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_000057.4(BLM):c.2407dup (p.Trp803fs)
HGVS:
  • NC_000015.10:g.90769438dup
  • NG_007272.1:g.57067dup
  • NM_000057.4:c.2407dupMANE SELECT
  • NM_001287246.2:c.2407dup
  • NM_001287247.2:c.2407dup
  • NM_001287248.2:c.1282dup
  • NP_000048.1:p.Trp803fs
  • NP_001274175.1:p.Trp803fs
  • NP_001274176.1:p.Trp803fs
  • NP_001274177.1:p.Trp428fs
  • LRG_20t1:c.2407dup
  • LRG_20:g.57067dup
  • NC_000015.9:g.91312668dup
  • NM_000057.2:c.2407dupT
  • NM_000057.3:c.2407dup
Protein change:
W428fs
Links:
dbSNP: rs367543012
NCBI 1000 Genomes Browser:
rs367543012
Molecular consequence:
  • NM_000057.4:c.2407dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001287246.2:c.2407dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001287247.2:c.2407dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001287248.2:c.1282dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Bloom syndrome (BLM)
Synonyms:
Bloom-Torre-Machacek syndrome; Growth deficiency, sun-sensitive, telangiectatic, hypo and hyperpigmented skin, predisposition to malignancy and chromosomal instability; MICROCEPHALY, GROWTH RESTRICTION, AND INCREASED SISTER CHROMATID EXCHANGE 1
Identifiers:
MONDO: MONDO:0008876; MedGen: C0005859; Orphanet: 125; OMIM: 210900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000058643GeneReviewsno assertion criteria providedPathogenic
(Feb 19, 2019)
germlineliterature only

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

SCV001132142Counsylno assertion criteria providedLikely pathogenic
(Apr 28, 2015)
unknownclinical testing

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

SCV001363837Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Oct 28, 2019)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, literature only
not providedunknownunknownnot providednot providednot providednot providednot 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

Bloom Syndrome.

Flanagan M, Cunniff CM.

2006 Mar 22 [updated 2019 Feb 14]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021.

PubMed [citation]
PMID:
20301572

Details of each submission

From GeneReviews, SCV000058643.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Counsyl, SCV001132142.1

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363837.1

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

Description

Variant summary: BLM c.2407dupT (p.Trp803LeufsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 251410 control chromosomes (gnomAD). c.2407dupT has been reported in the literature in individuals affected with Bloom Syndrome (German_2007). Two ClinVar submitters including a reputable database (Gene Reviews) (evaluation after 2014) cite the variant as pathogenic. Furthermore, Gene Reviews reports the variant as the second most common pathogenic variant for Bloom Syndrome in the Ashkenazi Jewish population (Flanagan_2019). Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Jun 14, 2021

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