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BLM

BLM RecQ like helicase, the group of RecQ like helicases

Basic information

Region (hg38): 15:90717345-90816166

Links

ENSG00000197299NCBI:641OMIM:604610HGNC:1058Uniprot:P54132AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Bloom syndrome (Definitive), mode of inheritance: AR
  • Bloom syndrome (Definitive), mode of inheritance: AR
  • osteosarcoma (Moderate), mode of inheritance: AR
  • Bloom syndrome (Moderate), mode of inheritance: AR
  • Bloom syndrome (Strong), mode of inheritance: AR
  • Bloom syndrome (Definitive), mode of inheritance: AR
  • Bloom syndrome (Supportive), mode of inheritance: AR
  • breast cancer (Disputed Evidence), mode of inheritance: AD
  • Bloom syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Bloom syndromeARAllergy/Immunology/Infectious; Dermatologic; Gastrointestinal; OncologicSurveillance and early diagnosis of malignancy could potentially be beneficial; Avoidance of ionizing radiation/DNA-damaging chemicals (as well as sun exposure) can reduce morbidity; Individuals may be susceptible to infections, and prompt treatment, as well as control of gastroesophageal reflux, which can be contributory, can be beneficialAllergy/Immunology/Infectious; Dermatologic; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic; Pulmonary5923432; 7386453; 7273457; 6705251; 3040954; 3808032; 3808031; 2721026; 1809225; 7585968; 8875252; 9062585; 9285778; 10464606; 11477604; 12242432; 15137905; 17407155; 18471088; 18974064; 20301572; 21815139; 22514588; 23028338; 23443610; 24118499
Variants may also be related to risk of malignancy in the general poulation

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BLM gene.

  • Bloom syndrome (3112 variants)
  • Hereditary cancer-predisposing syndrome (1954 variants)
  • not provided (339 variants)
  • not specified (162 variants)
  • Hereditary breast ovarian cancer syndrome (18 variants)
  • BLM-related condition (14 variants)
  • Ovarian cancer (11 variants)
  • Hereditary cancer (7 variants)
  • - (5 variants)
  • Inborn genetic diseases (4 variants)
  • Microcephaly (3 variants)
  • Familial cancer of breast;Endometrial carcinoma;Colorectal cancer (1 variants)
  • See cases (1 variants)
  • Hereditary disease (1 variants)
  • Olaparib response (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BLM gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
15
clinvar
770
clinvar
4
clinvar
789
missense
1
clinvar
3
clinvar
1854
clinvar
25
clinvar
6
clinvar
1889
nonsense
88
clinvar
27
clinvar
4
clinvar
119
start loss
2
clinvar
2
frameshift
146
clinvar
91
clinvar
6
clinvar
1
clinvar
1
clinvar
245
inframe indel
36
clinvar
1
clinvar
37
splice donor/acceptor (+/-2bp)
2
clinvar
62
clinvar
4
clinvar
68
splice region
3
59
92
4
158
non coding
2
clinvar
27
clinvar
271
clinvar
52
clinvar
352
Total 237 187 1946 1068 63

Highest pathogenic variant AF is 0.000171

Variants in BLM

This is a list of pathogenic ClinVar variants found in the BLM region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
15-90717375-G-T Bloom syndrome Uncertain significance (Jan 13, 2018)317402
15-90717380-C-T Bloom syndrome Uncertain significance (Jan 13, 2018)317403
15-90717386-T-A Bloom syndrome Uncertain significance (Jan 12, 2018)887590
15-90717412-G-C Bloom syndrome Uncertain significance (Jan 12, 2018)884448
15-90717416-C-T Bloom syndrome Uncertain significance (Jan 12, 2018)317404
15-90717440-G-A Hereditary cancer-predisposing syndrome Uncertain significance (Feb 19, 2021)1751005
15-90717456-G-C not specified • Bloom syndrome Benign (Dec 04, 2013)136515
15-90717714-G-C Benign (Jun 23, 2018)1291120
15-90717735-G-C Benign (Jun 23, 2018)1258065
15-90747136-G-C Benign (Jun 23, 2018)1258326
15-90747387-A-T Bloom syndrome Uncertain significance (Sep 04, 2020)990969
15-90747389-G-A Hereditary cancer-predisposing syndrome Uncertain significance (Mar 23, 2023)2562335
15-90747393-A-C Bloom syndrome Likely pathogenic (May 01, 2018)558084
15-90747393-A-G Bloom syndrome Uncertain significance (Jun 25, 2023)2777335
15-90747394-T-C Bloom syndrome • Hereditary cancer-predisposing syndrome Likely pathogenic (Jan 12, 2023)370566
15-90747396-G-T Bloom syndrome • Hereditary cancer-predisposing syndrome Uncertain significance (Feb 25, 2024)580296
15-90747397-C-A Hereditary cancer-predisposing syndrome Uncertain significance (Mar 04, 2021)1750979
15-90747399-G-A Bloom syndrome Uncertain significance (Jul 19, 2022)838635
15-90747399-G-GCT Bloom syndrome Likely pathogenic (Feb 12, 2023)2680184
15-90747401-T-C Bloom syndrome • Hereditary cancer-predisposing syndrome Likely benign (May 26, 2023)1161108
15-90747402-G-A Bloom syndrome Uncertain significance (May 29, 2022)1051649
15-90747402-G-C Bloom syndrome Uncertain significance (Nov 13, 2021)1488692
15-90747402-G-T Bloom syndrome Uncertain significance (Aug 26, 2021)1414390
15-90747403-T-A Bloom syndrome • Hereditary cancer-predisposing syndrome Uncertain significance (Nov 27, 2023)1462030
15-90747403-T-C not specified • Bloom syndrome • Hereditary cancer-predisposing syndrome • Hereditary cancer • BLM-related condition Conflicting classifications of pathogenicity (Jan 31, 2024)127473

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
BLMprotein_codingprotein_codingENST00000355112 2198302
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.54e-150.99912555401941257480.000772
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.8876647310.9080.00003629393
Missense in Polyphen207243.130.85143141
Synonymous1.142482720.9120.00001482626
Loss of Function3.143460.30.5640.00000292827

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001330.00130
Ashkenazi Jewish0.004180.00418
East Asian0.0005440.000544
Finnish0.00004620.0000462
European (Non-Finnish)0.0007960.000783
Middle Eastern0.0005440.000544
South Asian0.0004620.000457
Other0.0003380.000326

dbNSFP

Source: dbNSFP

Function
FUNCTION: ATP-dependent DNA helicase that unwinds single- and double-stranded DNA in a 3'-5' direction (PubMed:9388193, PubMed:24816114, PubMed:25901030). Participates in DNA replication and repair (PubMed:12019152, PubMed:21325134, PubMed:23509288). Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA (PubMed:21325134). Negatively regulates sister chromatid exchange (SCE) (PubMed:25901030). Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution (PubMed:25901030). Binds single-stranded DNA (ssDNA), forked duplex DNA and DNA Holliday junction (PubMed:20639533, PubMed:24257077, PubMed:25901030). {ECO:0000269|PubMed:12019152, ECO:0000269|PubMed:20639533, ECO:0000269|PubMed:21325134, ECO:0000269|PubMed:23509288, ECO:0000269|PubMed:24257077, ECO:0000269|PubMed:24816114, ECO:0000269|PubMed:25901030, ECO:0000269|PubMed:9388193}.;
Disease
DISEASE: Bloom syndrome (BLM) [MIM:210900]: An autosomal recessive disorder. It is characterized by proportionate pre- and postnatal growth deficiency, sun-sensitive telangiectatic hypo- and hyperpigmented skin, predisposition to malignancy, and chromosomal instability. {ECO:0000269|PubMed:10862105, ECO:0000269|PubMed:7585968, ECO:0000269|PubMed:9285778}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Fanconi anemia pathway - Homo sapiens (human);Homologous recombination - Homo sapiens (human);HDR through Single Strand Annealing (SSA);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Gene expression (Transcription);DNA Double-Strand Break Repair;Generic Transcription Pathway;SUMOylation of DNA damage response and repair proteins;Homology Directed Repair;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;SUMOylation;Fanconi anemia pathway;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Cell Cycle;Regulation of Telomerase;Processing of DNA double-strand break ends;ATM pathway;Presynaptic phase of homologous DNA pairing and strand exchange;Homologous DNA Pairing and Strand Exchange;Resolution of D-loop Structures through Holliday Junction Intermediates;Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA);Resolution of D-Loop Structures;HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

pRec
0.617

Intolerance Scores

loftool
0.959
rvis_EVS
-0.14
rvis_percentile_EVS
42.36

Haploinsufficiency Scores

pHI
0.760
hipred
Y
hipred_score
0.715
ghis
0.560

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.660

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Blm
Phenotype
neoplasm; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; embryo phenotype; immune system phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype;

Gene ontology

Biological process
regulation of cyclin-dependent protein serine/threonine kinase activity;resolution of meiotic recombination intermediates;double-strand break repair via homologous recombination;DNA double-strand break processing;DNA synthesis involved in DNA repair;strand displacement;DNA strand renaturation;DNA replication;DNA repair;double-strand break repair via nonhomologous end joining;DNA recombination;cellular response to DNA damage stimulus;mitotic G2 DNA damage checkpoint;response to X-ray;meiotic DNA double-strand break processing involved in reciprocal meiotic recombination;replication fork processing;DNA duplex unwinding;negative regulation of apoptotic process;G-quadruplex DNA unwinding;double-strand break repair via synthesis-dependent strand annealing;positive regulation of transcription, DNA-templated;negative regulation of DNA recombination;negative regulation of mitotic recombination;alpha-beta T cell differentiation;positive regulation of alpha-beta T cell proliferation;replication fork protection;protein complex oligomerization;protein homooligomerization;meiotic chromosome separation;negative regulation of cell division;telomeric D-loop disassembly;negative regulation of thymocyte apoptotic process;resolution of recombination intermediates;cellular response to ionizing radiation;cellular response to hydroxyurea;cellular response to camptothecin;regulation of DNA-dependent DNA replication;t-circle formation;negative regulation of double-strand break repair via single-strand annealing;positive regulation of double-strand break repair via homologous recombination
Cellular component
nuclear chromosome;chromosome, telomeric region;lateral element;nucleus;nucleoplasm;replication fork;chromosome;nucleolus;cytoplasm;cytosol;nuclear matrix;PML body;pronucleus
Molecular function
four-way junction DNA binding;Y-form DNA binding;bubble DNA binding;p53 binding;DNA binding;DNA helicase activity;single-stranded DNA binding;ATP-dependent DNA helicase activity;helicase activity;protein binding;ATP binding;ATP-dependent helicase activity;DNA-dependent ATPase activity;zinc ion binding;four-way junction helicase activity;ATPase activity;annealing helicase activity;protein homodimerization activity;ATP-dependent 3'-5' DNA helicase activity;G-quadruplex DNA binding;forked DNA-dependent helicase activity;telomeric D-loop binding;telomeric G-quadruplex DNA binding;8-hydroxy-2'-deoxyguanosine DNA binding