NM_000057.4(BLM):c.2242_2255del (p.Asn748fs) AND Bloom syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 11, 2022
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:: RCV002846630.3

Allele description [Variation Report for NM_000057.4(BLM):c.2242_2255del (p.Asn748fs)]

NM_000057.4(BLM):c.2242_2255del (p.Asn748fs)

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.2242_2255del (p.Asn748fs)

HGVS:

NC_000015.10:g.90766958_90766971del
NG_007272.1:g.54587_54600del
NM_000057.4:c.2242_2255delMANE SELECT
NM_001287246.2:c.2242_2255del
NM_001287247.2:c.2242_2255del
NM_001287248.2:c.1117_1130del
NP_000048.1:p.Asn748Valfs
NP_000048.1:p.Asn748fs
NP_001274175.1:p.Asn748fs
NP_001274176.1:p.Asn748fs
NP_001274177.1:p.Asn373fs
LRG_20t1:c.2242_2255del
LRG_20:g.54587_54600del
LRG_20p1:p.Asn748Valfs
NC_000015.9:g.91310186_91310199del
NC_000015.9:g.91310188_91310201del
NM_000057.2:c.2242_2255delAATATTTACCTCCA

Protein change:

N373fs

Molecular consequence:

NM_000057.4:c.2242_2255del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001287246.2:c.2242_2255del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001287247.2:c.2242_2255del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001287248.2:c.1117_1130del - frameshift variant - [Sequence Ontology: SO:0001589]

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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ilvE [Methanothermobacter thermautotrophicus str. Delta H]
ilvE [Methanothermobacter thermautotrophicus str. Delta H]
Gene ID:1471699

Gene
1471699[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003220607	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 11, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17407155, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003220607

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 11, 2022)

germline

clinical testing

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

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

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003220607.2

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

Description

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 variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn748Valfs*22) 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).

#	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

Last Updated: Sep 29, 2024

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