NM_000057.4(BLM):c.1429_1432del (p.Thr477fs) AND Bloom syndrome

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 21, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000668814.7

Allele description [Variation Report for NM_000057.4(BLM):c.1429_1432del (p.Thr477fs)]

NM_000057.4(BLM):c.1429_1432del (p.Thr477fs)

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.1429_1432del (p.Thr477fs)

HGVS:

NC_000015.10:g.90760802_90760805del
NG_007272.1:g.48431_48434del
NM_000057.4:c.1429_1432delMANE SELECT
NM_001287246.2:c.1429_1432del
NM_001287247.2:c.1429_1432del
NM_001287248.2:c.304_307del
NP_000048.1:p.Thr477fs
NP_001274175.1:p.Thr477fs
NP_001274176.1:p.Thr477fs
NP_001274177.1:p.Thr102fs
LRG_20t1:c.1429_1432del
LRG_20:g.48431_48434del
NC_000015.9:g.91304030_91304033del
NC_000015.9:g.91304032_91304035del
NM_000057.2:c.1429_1432delACAG

Protein change:

T102fs

Links:

dbSNP: rs1555419873

NCBI 1000 Genomes Browser:

rs1555419873

Molecular consequence:

NM_000057.4:c.1429_1432del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001287246.2:c.1429_1432del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001287247.2:c.1429_1432del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001287248.2:c.304_307del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Bloom syndrome (BLM)
Synonyms:: Bloom-Torre-Machacek syndrome
Identifiers:: MONDO: MONDO:0008876; MedGen: C0005859; Orphanet: 125; OMIM: 210900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000793478	Counsyl	no assertion criteria provided	Likely pathogenic (Aug 24, 2017)	unknown	clinical testing
SCV002946257	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 8, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17407155, 28492532
SCV005058145	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 21, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000793478

Counsyl

no assertion criteria provided

Likely pathogenic
(Aug 24, 2017)

unknown

clinical testing

SCV002946257

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 8, 2022)

germline

clinical testing

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

SCV005058145

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 21, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

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. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000793478.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002946257.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

ClinVar contains an entry for this variant (Variation ID: 553382). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with BLM-related conditions. This sequence change creates a premature translational stop signal (p.Thr477Aspfs*24) 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 not present in population databases (gnomAD no frequency).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV005058145.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 29, 2025

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