NM_000057.4(BLM):c.2887C>T (p.His963Tyr) AND Bloom syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 18, 2023
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:: RCV001869452.4

Allele description [Variation Report for NM_000057.4(BLM):c.2887C>T (p.His963Tyr)]

NM_000057.4(BLM):c.2887C>T (p.His963Tyr)

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.2887C>T (p.His963Tyr)

HGVS:

NC_000015.10:g.90790712C>T
NG_007272.1:g.78341C>T
NM_000057.4:c.2887C>TMANE SELECT
NM_001287246.2:c.2887C>T
NM_001287247.2:c.2887C>T
NM_001287248.2:c.1762C>T
NP_000048.1:p.His963Tyr
NP_001274175.1:p.His963Tyr
NP_001274176.1:p.His963Tyr
NP_001274177.1:p.His588Tyr
LRG_20t1:c.2887C>T
LRG_20:g.78341C>T
NC_000015.9:g.91333942C>T
NM_000057.2:c.2887C>T
NM_000057.3:c.2887C>T

Protein change:

H588Y

Links:

dbSNP: rs367543023

NCBI 1000 Genomes Browser:

rs367543023

Molecular consequence:

NM_000057.4:c.2887C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001287246.2:c.2887C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001287247.2:c.2887C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001287248.2:c.1762C>T - 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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Human elongation factor-1 alpha (ef-1) mRNA, 3' end
Human elongation factor-1 alpha (ef-1) mRNA, 3' end
gi|1220310|gb|L10340.1|HUMHS1X

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002197534	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 18, 2023)	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

SCV002197534

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 18, 2023)

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002197534.3

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

Description

This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 963 of the BLM protein (p.His963Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Bloom syndrome (PMID: 17407155). ClinVar contains an entry for this variant (Variation ID: 1330099). 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 expected to disrupt BLM protein function. 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

Last Updated: Sep 29, 2024

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