NM_000057.4(BLM):c.959+1_959+9del AND Bloom syndrome

Clinical significance:Likely pathogenic (Last evaluated: Apr 8, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000672659.2

Allele description [Variation Report for NM_000057.4(BLM):c.959+1_959+9del]

NM_000057.4(BLM):c.959+1_959+9del

Gene:
BLM:BLM RecQ like helicase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_000057.4(BLM):c.959+1_959+9del
HGVS:
  • NC_000015.10:g.90751947_90751955del
  • NG_007272.1:g.39576_39584del
  • NM_000057.4:c.959+1_959+9delMANE SELECT
  • NM_001287246.2:c.959+1_959+9del
  • NM_001287247.2:c.959+1_959+9del
  • NM_001287248.2:c.-333+1_-333+9del
  • LRG_20t1:c.959+1_959+9del
  • LRG_20t1:c.959+1_959+9del9
  • LRG_20:g.39576_39584del
  • NC_000015.9:g.91295177_91295185del
  • NM_000057.2:c.959+1_959+9del9
  • NM_000057.3:c.959+1_959+9del
Links:
dbSNP: rs765061205
NCBI 1000 Genomes Browser:
rs765061205
Molecular consequence:
  • NM_000057.4:c.959+1_959+9del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001287246.2:c.959+1_959+9del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001287247.2:c.959+1_959+9del - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001287248.2:c.-333+1_-333+9del - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV000797786Counsylcriteria provided, single submitter
Likely pathogenic
(Feb 13, 2018)
unknownclinical testing

Citation Link,

SCV000823834Invitaecriteria provided, single submitter
Likely pathogenic
(Apr 8, 2018)
germlineclinical testing

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

Summary from all submissions

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

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Counsyl, SCV000797786.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000823834.1

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

Description

This sequence change affects a donor splice site in intron 4 of the BLM gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with BLM-related disease. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Nov 27, 2021

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