NM_000057.4(BLM):c.98+1G>T AND Bloom syndrome

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Oct 23, 2020)

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:
RCV000410622.6

Allele description [Variation Report for NM_000057.4(BLM):c.98+1G>T]

NM_000057.4(BLM):c.98+1G>T

Gene:
BLM:BLM RecQ like helicase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q26.1
Genomic location:
Preferred name:
NM_000057.4(BLM):c.98+1G>T
HGVS:
  • NC_000015.10:g.90747491G>T
  • NG_007272.1:g.35120G>T
  • NM_000057.4:c.98+1G>TMANE SELECT
  • NM_001287246.2:c.98+1G>T
  • NM_001287247.2:c.98+1G>T
  • NM_001287248.2:c.-1194+1G>T
  • LRG_20t1:c.98+1G>T
  • LRG_20:g.35120G>T
  • NC_000015.9:g.91290721G>T
  • NM_000057.2:c.98+1G>T
  • NM_000057.3:c.98+1G>T
Links:
dbSNP: rs750293380
NCBI 1000 Genomes Browser:
rs750293380
Molecular consequence:
  • NM_000057.4:c.98+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001287246.2:c.98+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001287247.2:c.98+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001287248.2:c.-1194+1G>T - 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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000485449Counsylcriteria provided, single submitter
Likely pathogenic
(Dec 13, 2015)
unknownclinical testing

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

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV000893387Fulgent Genetics,Fulgent Geneticscriteria provided, single submitter
Pathogenic
(Oct 31, 2018)
unknownclinical testing

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

SCV000916682Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely pathogenic
(Jul 9, 2018)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV000940882Invitaecriteria provided, single submitter
Likely pathogenic
(Oct 23, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Expanding preconception carrier screening for the Jewish population using high throughput microfluidics technology and next generation sequencing.

Gal M, Khermesh K, Barak M, Lin M, Lahat H, Reznik Wolf H, Lin M, Pras E, Levanon EY.

BMC Med Genomics. 2016 May 13;9(1):24. doi: 10.1186/s12920-016-0184-7.

PubMed [citation]
PMID:
27175728
PMCID:
PMC4865987
See all PubMed Citations (6)

Details of each submission

From Counsyl, SCV000485449.1

#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 Fulgent Genetics,Fulgent Genetics, SCV000893387.1

#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, SCV000916682.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: BLM c.98+1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. These predictions are supported by RT-PCR studies that showed exon 2 skipping, though the data was not available for review (German_2007). The variant allele was found at a frequency of 1.3e-05 in 225466 control chromosomes. c.98+1G>T has been reported in the literature in one individual affected with Bloom Syndrome, which does not allow strong conclusions about variant significance. A different variant at the same location (c.98+1G>A) has also been implicated in Bloom Syndrome. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

From Invitae, SCV000940882.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change affects a donor splice site in intron 2 of the BLM gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs750293380, ExAC 0.003%). This variant has been observed in an individual affected with clinical features of Bloom syndrome (PMID: 17407155). ClinVar contains an entry for this variant (Variation ID: 370200). 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: Jun 14, 2021

Support Center