NM_000057.4(BLM):c.3731T>C (p.Val1244Ala) AND Bloom syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 26, 2021
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:: RCV002043894.5

Allele description [Variation Report for NM_000057.4(BLM):c.3731T>C (p.Val1244Ala)]

NM_000057.4(BLM):c.3731T>C (p.Val1244Ala)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

15q26.1

Genomic location:

Preferred name:

NM_000057.4(BLM):c.3731T>C (p.Val1244Ala)

HGVS:

NC_000015.10:g.90804339T>C
NG_007272.1:g.91968T>C
NM_000057.4:c.3731T>CMANE SELECT
NM_001287246.2:c.3731T>C
NM_001287247.2:c.3359-4798T>C
NM_001287248.2:c.2606T>C
NP_000048.1:p.Val1244Ala
NP_001274175.1:p.Val1244Ala
NP_001274177.1:p.Val869Ala
LRG_20:g.91968T>C
NC_000015.9:g.91347569T>C

Protein change:

V1244A

Links:

dbSNP: rs771117920

NCBI 1000 Genomes Browser:

rs771117920

Molecular consequence:

NM_001287247.2:c.3359-4798T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000057.4:c.3731T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001287246.2:c.3731T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001287248.2:c.2606T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002312692	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 26, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20639533, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002312692

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 26, 2021)

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

Structure and function of the regulatory HRDC domain from human Bloom syndrome protein.

Kim YM, Choi BS.

Nucleic Acids Res. 2010 Nov;38(21):7764-77. doi: 10.1093/nar/gkq586. Epub 2010 Jul 17.

PubMed [citation]

PMID:: 20639533
PMCID:: PMC2995041

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 Invitae, SCV002312692.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BLM protein function (PMID: 20639533). This variant has not been reported in the literature in individuals with BLM-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 1244 of the BLM protein (p.Val1244Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine.

#	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: Mar 5, 2024

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