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NM_000057.4(BLM):c.1220G>C (p.Arg407Thr) AND Bloom syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Jan 11, 2024
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000811037.11

Allele description [Variation Report for NM_000057.4(BLM):c.1220G>C (p.Arg407Thr)]

NM_000057.4(BLM):c.1220G>C (p.Arg407Thr)

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.1220G>C (p.Arg407Thr)
HGVS:
  • NC_000015.10:g.90760279G>C
  • NG_007272.1:g.47908G>C
  • NM_000057.4:c.1220G>CMANE SELECT
  • NM_001287246.2:c.1220G>C
  • NM_001287247.2:c.1220G>C
  • NM_001287248.2:c.95G>C
  • NP_000048.1:p.Arg407Thr
  • NP_001274175.1:p.Arg407Thr
  • NP_001274176.1:p.Arg407Thr
  • NP_001274177.1:p.Arg32Thr
  • LRG_20:g.47908G>C
  • NC_000015.9:g.91303509G>C
  • NM_000057.2:c.1220G>C
  • NM_000057.3:c.1220G>C
Protein change:
R32T
Links:
dbSNP: rs1350192744
NCBI 1000 Genomes Browser:
rs1350192744
Molecular consequence:
  • NM_000057.4:c.1220G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287246.2:c.1220G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287247.2:c.1220G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001287248.2:c.95G>C - missense variant - [Sequence Ontology: SO:0001583]

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
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
SCV000951282Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 11, 2024)
germlineclinical testing

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

SCV002090016Natera, Inc.
no assertion criteria provided
Uncertain significance
(Sep 14, 2020)
germlineclinical testing

Summary from all submissions

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

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000951282.6

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

Description

This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 407 of the BLM protein (p.Arg407Thr). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 654963). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change results in skipping of exon 6 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.

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

From Natera, Inc., SCV002090016.1

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

Last Updated: Sep 29, 2024