NM_000975.5(RPL11):c.7-1G>T AND Diamond-Blackfan anemia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 4, 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:: RCV001064457.8

Allele description [Variation Report for NM_000975.5(RPL11):c.7-1G>T]

NM_000975.5(RPL11):c.7-1G>T

Gene:

RPL11:ribosomal protein L11 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.11

Genomic location:

Preferred name:

NM_000975.5(RPL11):c.7-1G>T

HGVS:

NC_000001.11:g.23692608G>T
NG_011741.2:g.5830G>T
NM_000975.5:c.7-1G>TMANE SELECT
NM_001199802.1:c.7-4G>T
LRG_1140t1:c.7-1G>T
LRG_1140:g.5830G>T
NC_000001.10:g.24019098G>T
NM_000975.3:c.7-1G>T

Links:

dbSNP: rs1644507858

NCBI 1000 Genomes Browser:

rs1644507858

Molecular consequence:

NM_001199802.1:c.7-4G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000975.5:c.7-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Diamond-Blackfan anemia
Synonyms:: Blackfan Diamond syndrome; Anemia congenital erythroid hypoplastic; Aregenerative anemia chronic congenital; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015253; MeSH: D029503; MedGen: C1260899; Orphanet: 124; OMIM: PS105650; Human Phenotype Ontology: HP:0004810

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Citrobacter sp. P061 16S ribosomal RNA gene, partial sequence
Citrobacter sp. P061 16S ribosomal RNA gene, partial sequence
gi|460479531|gb|KC252802.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001229361	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 4, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 19061985, 19773262, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001229361

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 4, 2022)

germline

clinical testing

PubMed (4)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients.

Gazda HT, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Schneider H, Darras N, Hasman C, Sieff CA, Newburger PE, Ball SE, Niewiadomska E, Matysiak M, Zaucha JM, Glader B, Niemeyer C, Meerpohl JJ, Atsidaftos E, Lipton JM, Gleizes PE, Beggs AH.

Am J Hum Genet. 2008 Dec;83(6):769-80. doi: 10.1016/j.ajhg.2008.11.004.

PubMed [citation]

PMID:: 19061985
PMCID:: PMC2668101

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001229361.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is not present in population databases (gnomAD no frequency). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, and lead to utilization of a cryptic splice site located 3 nucleotides downstream. Use of this cryptic splice site would lead to an in-frame loss of 1 amino acid, but would otherwise preserve the integrity of the reading frame. An exon lacking this amino acid naturally occurs in an alternate isoform of RPL11 (NM_001199802.1). This prediction has not been confirmed by published transcriptional studies, but suggests that the clinical significance of this splice variant may be uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 858562). This variant has not been reported in the literature in individuals affected with RPL11-related conditions. This sequence change affects an acceptor splice site in intron 1 of the RPL11 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RPL11 are known to be pathogenic (PMID: 19061985, 19773262).

#	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: May 12, 2024

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