NM_000057.4(BLM):c.2488dup (p.Thr830fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 7, 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:: RCV002426544.2

Allele description [Variation Report for NM_000057.4(BLM):c.2488dup (p.Thr830fs)]

NM_000057.4(BLM):c.2488dup (p.Thr830fs)

Gene:

BLM:BLM RecQ like helicase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

15q26.1

Genomic location:

Preferred name:

NM_000057.4(BLM):c.2488dup (p.Thr830fs)

HGVS:

NC_000015.10:g.90769519dup
NC_000015.9:g.91312748_91312749insA
NG_007272.1:g.57148dup
NM_000057.4:c.2488dupMANE SELECT
NM_001287246.2:c.2488dup
NM_001287247.2:c.2488dup
NM_001287248.2:c.1363dup
NP_000048.1:p.Thr830fs
NP_001274175.1:p.Thr830fs
NP_001274176.1:p.Thr830fs
NP_001274177.1:p.Thr455fs
LRG_20t1:c.2488_2489dup
LRG_20:g.57148dup
NC_000015.9:g.91312748_91312749insA
NC_000015.9:g.91312749dup
NC_000015.9:g.91312749dupA
NM_000057.2:c.2488dupA
NM_000057.3:c.2488dup
NM_000057.3:c.2488dupA

Protein change:

T455fs

Links:

Counsyl: 25547; dbSNP: rs367543019

NCBI 1000 Genomes Browser:

rs367543019

Molecular consequence:

NM_000057.4:c.2488dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001287246.2:c.2488dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001287247.2:c.2488dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001287248.2:c.1363dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002741776	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Sep 7, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17407155, 26247052 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002741776

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Sep 7, 2022)

germline

clinical testing

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

Citation Link

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

A rigorous approach for selection of optimal variant sets for carrier screening with demonstration of clinical utility.

Perreault-Micale C, Davie J, Breton B, Hallam S, Greger V.

Mol Genet Genomic Med. 2015 Jul;3(4):363-73. doi: 10.1002/mgg3.148. Epub 2015 Apr 23.

PubMed [citation]

PMID:: 26247052
PMCID:: PMC4521971

Details of each submission

From Ambry Genetics, SCV002741776.2

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

Description

The c.2488dupA pathogenic mutation, located in coding exon 11 of the BLM gene, results from a duplication of A at nucleotide position 2488, causing a translational frameshift with a predicted alternate stop codon (p.T830Nfs*5). This alteration was reported in an individual with a second protein truncating BLM alteration and a clinical diagnosis of Bloom syndrome (German J et al. Hum. Mutat., 2007 Aug;28:743-53). In addition to the information presented in the literature, since 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.

#	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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