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

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Jan 25, 2024
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:: RCV000536540.12

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:: 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000623326	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 25, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 35264596, 23129629, 28492532
SCV000838988	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (Jul 2, 2018)	unknown	clinical testing	Citation Link,
SCV000898549	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002789266	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 19, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Detection of germline variants in Brazilian breast cancer patients using multigene panel testing.

Guindalini RSC, Viana DV, Kitajima JPFW, Rocha VM, López RVM, Zheng Y, Freitas É, Monteiro FPM, Valim A, Schlesinger D, Kok F, Olopade OI, Folgueira MAAK.

Sci Rep. 2022 Mar 9;12(1):4190. doi: 10.1038/s41598-022-07383-1.

PubMed [citation]

PMID:: 35264596
PMCID:: PMC8907244

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000623326.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1331 of the BLM protein (p.Arg1331Gly). This variant is present in population databases (rs150631940, gnomAD 0.02%). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 127507). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BLM protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect BLM function (PMID: 23129629). 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.

#	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

From Mendelics, SCV000838988.2

#	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 Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago, SCV000898549.2

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

Description

BLM NM_000057 exon 21 p.Arg1331Gly (c.3991A>G):This variant has not been reported in the literature but is present in 5/24038 African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs150631940). This variant is present in ClinVar (Variation ID:127507). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. Functional studies suggest that this variant may not impact the protein (Mirzaei 2012 PMID:231296269). However, these studies may not accurately represent in vivo biological function. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002789266.1

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

#	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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine