NM_000057.4(BLM):c.3028del (p.Asp1010fs) AND Bloom syndrome

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Nov 3, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000169440.7

Allele description [Variation Report for NM_000057.4(BLM):c.3028del (p.Asp1010fs)]

NM_000057.4(BLM):c.3028del (p.Asp1010fs)

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.3028del (p.Asp1010fs)
HGVS:
  • NC_000015.10:g.90794175del
  • NG_007272.1:g.81804del
  • NM_000057.4:c.3028delMANE SELECT
  • NM_001287246.2:c.3028del
  • NM_001287247.2:c.3028del
  • NM_001287248.2:c.1903del
  • NP_000048.1:p.Asp1010fs
  • NP_001274175.1:p.Asp1010fs
  • NP_001274176.1:p.Asp1010fs
  • NP_001274177.1:p.Asp635fs
  • LRG_20t1:c.3028del
  • LRG_20:g.81804del
  • NC_000015.9:g.91337405del
  • NM_000057.2:c.3028del
  • NM_000057.2:c.3028delG
  • NM_000057.3:c.3028del
  • NM_000057.3:c.3028delG
Protein change:
D1010fs
Links:
dbSNP: rs780379121
NCBI 1000 Genomes Browser:
rs780379121
Molecular consequence:
  • NM_000057.4:c.3028del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001287246.2:c.3028del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001287247.2:c.3028del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001287248.2:c.1903del - 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
SCV000220857Counsylcriteria provided, single submitter
Likely pathogenic
(Nov 6, 2014)
unknownliterature only

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

Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015),

Citation Link,

SCV000623297Invitaecriteria provided, single submitter
Pathogenic
(Mar 20, 2020)
germlineclinical testing

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

SCV001363838Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Jun 17, 2019)
germlineclinical testing

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

Citation Link,

SCV002010757Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresdencriteria provided, single submitter
Pathogenic
(Nov 3, 2021)
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
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedliterature only

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

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
See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000220857.1

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

From Invitae, SCV000623297.5

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

Description

This sequence change creates a premature translational stop signal (p.Asp1010Metfs*24) in the BLM gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs780379121, ExAC 0.003%). This variant has been reported in individuals affected with Bloom syndrome (PMID: 17407155). ClinVar contains an entry for this variant (Variation ID: 189048). Loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). For these reasons, this variant has been classified as Pathogenic.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363838.1

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

Description

Variant summary: BLM c.3028delG (p.Asp1010MetfsX24) 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 1.2e-05 in 248358 control chromosomes (gnomAD). c.3028delG has been reported in the literature in a homozygous and compound heterozygote individuals affected with Bloom Syndrome (German_2007). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as pathogenic. 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

From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV002010757.1

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

Last Updated: Nov 27, 2021

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