NM_000057.4(BLM):c.3991A>G (p.Arg1331Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 6, 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:: RCV001021594.4

Allele description [Variation Report for NM_000057.4(BLM):c.3991A>G (p.Arg1331Gly)]

NM_000057.4(BLM):c.3991A>G (p.Arg1331Gly)

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.3991A>G (p.Arg1331Gly)

Other names:

p.R1331G:AGA>GGA

HGVS:

NC_000015.10:g.90811321A>G
NG_007272.1:g.98950A>G
NM_000057.4:c.3991A>GMANE SELECT
NM_001287246.2:c.3991A>G
NM_001287247.2:c.3598A>G
NM_001287248.2:c.2866A>G
NP_000048.1:p.Arg1331Gly
NP_001274175.1:p.Arg1331Gly
NP_001274176.1:p.Arg1200Gly
NP_001274177.1:p.Arg956Gly
LRG_20t1:c.3991A>G
LRG_20:g.98950A>G
NC_000015.9:g.91354551A>G
NM_000057.2:c.3991A>G
NM_000057.3:c.3991A>G

Protein change:

R1200G

Links:

dbSNP: rs150631940

NCBI 1000 Genomes Browser:

rs150631940

Molecular consequence:

NM_000057.4:c.3991A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001287246.2:c.3991A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001287247.2:c.3598A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001287248.2:c.2866A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001183230	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Sep 6, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23129629, 28944238 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001183230

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Sep 6, 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

Non-Bloom syndrome-associated partial and total loss-of-function variants of BLM helicase.

Mirzaei H, Schmidt KH.

Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19357-62. doi: 10.1073/pnas.1210304109. Epub 2012 Nov 5.

PubMed [citation]

PMID:: 23129629
PMCID:: PMC3511070

Targeted sequencing of 36 known or putative colorectal cancer susceptibility genes.

DeRycke MS, Gunawardena S, Balcom JR, Pickart AM, Waltman LA, French AJ, McDonnell S, Riska SM, Fogarty ZC, Larson MC, Middha S, Eckloff BW, Asmann YW, Ferber MJ, Haile RW, Gallinger S, Clendenning M, Rosty C, Win AK, Buchanan DD, Hopper JL, Newcomb PA, et al.

Mol Genet Genomic Med. 2017 Sep;5(5):553-569. doi: 10.1002/mgg3.317.

PubMed [citation]

PMID:: 28944238
PMCID:: PMC5606870

Details of each submission

From Ambry Genetics, SCV001183230.4

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

Description

The p.R1331G variant (also known as c.3991A>G), located in coding exon 20 of the BLM gene, results from an A to G substitution at nucleotide position 3991. The arginine at codon 1331 is replaced by glycine, an amino acid with dissimilar properties. In a study using a humanized yeast model, this alteration was found to perform similar to wildtype when exposed to a DNA-damaging agent (Mirzaei H et al. Proc. Natl. Acad. Sci. U.S.A., 2012 Nov;109:19357-62). This alteration was identified in an individual diagnosed with colorectal cancer (DeRycke MS et al. Mol Genet Genomic Med, 2017 Sep;5:553-569). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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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