NM_000057.4(BLM):c.3499del (p.Ala1167fs) AND Bloom syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Oct 2, 2020
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:: RCV000665331.6

Allele description [Variation Report for NM_000057.4(BLM):c.3499del (p.Ala1167fs)]

NM_000057.4(BLM):c.3499del (p.Ala1167fs)

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.3499del (p.Ala1167fs)

HGVS:

NC_000015.10:g.90803661del
NG_007272.1:g.91290del
NM_000057.4:c.3499delMANE SELECT
NM_001287246.2:c.3499del
NM_001287247.2:c.3358+5324del
NM_001287248.2:c.2374del
NP_000048.1:p.Ala1167fs
NP_001274175.1:p.Ala1167fs
NP_001274177.1:p.Ala792fs
LRG_20t1:c.3499del
LRG_20:g.91290del
NC_000015.9:g.91346890del
NC_000015.9:g.91346891del
NM_000057.2:c.3499delG

Protein change:

A1167fs

Links:

dbSNP: rs1555424305

NCBI 1000 Genomes Browser:

rs1555424305

Molecular consequence:

NM_000057.4:c.3499del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001287246.2:c.3499del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001287248.2:c.2374del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001287247.2:c.3358+5324del - intron variant - [Sequence Ontology: SO:0001627]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000789435	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Jan 31, 2017)	unknown	clinical testing	Citation Link,
SCV001585508	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 2, 2020)	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

SCV000789435

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Jan 31, 2017)

unknown

clinical testing

Citation Link,

SCV001585508

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 2, 2020)

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
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

Details of each submission

From Counsyl, SCV000789435.1

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

#	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, SCV001585508.4

#	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. Loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). This variant has not been reported in the literature in individuals with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 550553). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ala1167Argfs*5) in the BLM gene. It is expected to result in an absent or disrupted protein product.

#	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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