ClinVar Genomic variation as it relates to human health
NM_000057.4(BLM):c.772_773del (p.Leu258fs)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000057.4(BLM):c.772_773del (p.Leu258fs)
Variation ID: 42092 Accession: VCV000042092.21
- Type and length
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Microsatellite, 2 bp
- Location
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Cytogenetic: 15q26.1 15: 90750036-90750037 (GRCh38) [ NCBI UCSC ] 15: 91293266-91293267 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline May 3, 2013 May 1, 2024 Jan 6, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000057.4:c.772_773del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000048.1:p.Leu258fs frameshift NM_000057.2:c.772_773delCT NM_000057.3:c.772_773del NM_001287246.2:c.772_773del NP_001274175.1:p.Leu258fs frameshift NM_001287247.2:c.772_773del NP_001274176.1:p.Leu258fs frameshift NM_001287248.2:c.-524CT[2] 5 prime UTR NC_000015.10:g.90750036CT[2] NC_000015.9:g.91293266CT[2] NG_007272.1:g.37665CT[2] LRG_20:g.37665CT[2] LRG_20t1:c.772_773del - Protein change
- L258fs
- Other names
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- Canonical SPDI
- NC_000015.10:90750035:CTCTCT:CTCT
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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BLM | - | - |
GRCh38 GRCh37 |
4287 | 4338 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Jan 6, 2024 | RCV000034918.18 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 19, 2021 | RCV002399367.2 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jul 6, 2023 | RCV003162295.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Oct 07, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV003915236.1
First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023 |
Comment:
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Identified in the heterozygous state in individuals with breast, ovarian, or colorectal cancer (Kanchi et al., 2014; Sun et al., 2017; Huang et al., 2018); This variant is associated with the following publications: (PMID: 26247052, 17407155, 24448499, 28724667, 29625052, 29783825, 29478780, 31721094) (less)
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Pathogenic
(Sep 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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Bloom syndrome
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004210854.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Apr 24, 2017)
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criteria provided, single submitter
Method: clinical testing
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Bloom syndrome
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000694481.1
First in ClinVar: May 30, 2015 Last updated: May 30, 2015 |
Comment:
Variant summary: The BLM c.772_773delCT (p.Leu258Glufs) variant results in a premature termination codon, predicted to cause a truncated or absent BLM protein due to nonsense … (more)
Variant summary: The BLM c.772_773delCT (p.Leu258Glufs) variant results in a premature termination codon, predicted to cause a truncated or absent BLM protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.2207_2212delinsTAGATTC (p.Tyr736fs) and c.1642C>T (p.Gln548X)). One in silico tool predicts a damaging outcome for this variant. This variant was found in 5/119222 control chromosomes at a frequency of 0.0000419, which does not exceed the estimated maximal expected allele frequency of a pathogenic BLM variant (0.0035355). The variant has been reported in at least one homozygous affected individual in the literature. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as "pathogenic." (less)
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Pathogenic
(Mar 12, 2021)
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criteria provided, single submitter
Method: clinical testing
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Bloom syndrome
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
inherited
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New York Genome Center
Study: CSER-NYCKidSeq
Accession: SCV002098975.1 First in ClinVar: Feb 26, 2022 Last updated: Feb 26, 2022 |
Clinical Features:
Seizure (present) , Intellectual disability (present) , Autism (present) , Attention deficit hyperactivity disorder (present)
Secondary finding: no
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Likely pathogenic
(Jun 04, 2014)
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criteria provided, single submitter
Method: literature only
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Bloom syndrome
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220377.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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Pathogenic
(Jul 06, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004222505.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
This variant alters the translational reading frame of the BLM mRNA and causes the premature termination of BLM protein synthesis. In the published literature, this … (more)
This variant alters the translational reading frame of the BLM mRNA and causes the premature termination of BLM protein synthesis. In the published literature, this variant has been reported in individuals with breast cancer (PMID: 36315097 (2022), 28724667 (2017)), rectal cancer (PMID: 29625052 (2018)), colorectal cancer (PMID: 29478780 (2018)), lung cancer (PMID: 35273153 (2022), 31721094 (2020)), and astrocytoma (PMID: 32783018 (2019), 31133068 (2019)). This variant has also been observed in individuals with Bloom Syndrome (PMID: 29783825 (2018), 17407155 (2007)). The frequency of this variant in the general population, 0.00016 (4/24446 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. (less)
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Pathogenic
(Jan 06, 2024)
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criteria provided, single submitter
Method: clinical testing
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Bloom syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000749564.7
First in ClinVar: May 03, 2018 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Leu258Glufs*7) in the BLM gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Leu258Glufs*7) in the BLM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). This variant is present in population databases (rs760209332, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with Bloom syndrome and breast and ovarian cancer (PMID: 17407155, 24448499, 28724667). This variant is also known as c.768_769del, p.D256fs. ClinVar contains an entry for this variant (Variation ID: 42092). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jan 19, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002669910.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.772_773delCT pathogenic mutation, located in coding exon 2 of the BLM gene, results from a deletion of two nucleotides at nucleotide positions 772 to … (more)
The c.772_773delCT pathogenic mutation, located in coding exon 2 of the BLM gene, results from a deletion of two nucleotides at nucleotide positions 772 to 773, causing a translational frameshift with a predicted alternate stop codon (p.L258Efs*7). This mutation has been reported in the homozygous and compound heterozygous states in patients with Bloom syndrome (German J et al. Hum Mutat, 2007 Aug;28:743-53; Wu ML et al. Zhonghua Er Ke Za Zhi, 2018 May;56:373-376). This mutation has also been reported in a patient with ovarian cancer (Kanchi KL et al. Nat Commun, 2014;5:3156). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
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Pathogenic
(Mar 17, 2017)
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no assertion criteria provided
Method: clinical testing
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Bloom syndrome
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002089970.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Somatic inactivation of breast cancer predisposition genes in tumors associated with pathogenic germline variants. | Lim BWX | Journal of the National Cancer Institute | 2023 | PMID: 36315097 |
Clinical and genomic features of Chinese lung cancer patients with germline mutations. | Peng W | Nature communications | 2022 | PMID: 35273153 |
Case Report: Diabetes in Chinese Bloom Syndrome. | Deng M | Frontiers in endocrinology | 2021 | PMID: 34177791 |
Spectrum of Pathogenic Germline Mutations in Chinese Lung Cancer Patients through Next-Generation Sequencing. | Tian P | Pathology oncology research : POR | 2020 | PMID: 31721094 |
Pediatric Somatic Tumor Sequencing Identifies Underlying Cancer Predisposition. | MacFarland SP | JCO precision oncology | 2019 | PMID: 32783018 |
Clinical utility of custom-designed NGS panel testing in pediatric tumors. | Surrey LF | Genome medicine | 2019 | PMID: 31133068 |
[Clinical and molecular analysis of two Chinese siblings with Bloom syndrome]. | Wu ML | Zhonghua er ke za zhi = Chinese journal of pediatrics | 2018 | PMID: 29783825 |
Pathogenic Germline Variants in 10,389 Adult Cancers. | Huang KL | Cell | 2018 | PMID: 29625052 |
Inherited DNA-Repair Defects in Colorectal Cancer. | AlDubayan SH | American journal of human genetics | 2018 | PMID: 29478780 |
Germline Mutations in Cancer Susceptibility Genes in a Large Series of Unselected Breast Cancer Patients. | Sun J | Clinical cancer research : an official journal of the American Association for Cancer Research | 2017 | PMID: 28724667 |
A rigorous approach for selection of optimal variant sets for carrier screening with demonstration of clinical utility. | Perreault-Micale C | Molecular genetics & genomic medicine | 2015 | PMID: 26247052 |
Integrated analysis of germline and somatic variants in ovarian cancer. | Kanchi KL | Nature communications | 2014 | PMID: 24448499 |
Syndrome-causing mutations of the BLM gene in persons in the Bloom's Syndrome Registry. | German J | Human mutation | 2007 | PMID: 17407155 |
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Text-mined citations for rs367543013 ...
HelpRecord last updated May 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.