NR_003051.4(RMRP):n.-20_-1dup AND Anauxetic dysplasia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 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:: RCV001243700.13

Allele description [Variation Report for NR_003051.4(RMRP):n.-20_-1dup]

NR_003051.4(RMRP):n.-20_-1dup

Gene:

RMRP:RNA component of mitochondrial RNA processing endoribonuclease [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

9p13.3

Genomic location:

Preferred name:

NR_003051.4(RMRP):n.-20_-1dup

HGVS:

NC_000009.11:g.35658017_35658036dup20
NC_000009.12:g.35658020_35658039dup
NG_017041.1:g.4980_4999dup
NG_033120.1:g.4731_4750dup
NG_116211.1:g.556_575dup
LRG_163t1:n.-21_-2dup
LRG_163:g.4980_4999dup
NC_000009.11:g.35658016_35658017insCGTCCTCAGCTTCACAGAGT
NC_000009.11:g.35658017_35658036dup
NC_000009.11:g.35658017_35658036dup20
NR_003051.3:n.-21_-2dup
NR_003051.4:n.-20_-1dupMANE SELECT

Links:

dbSNP: rs1554651403

NCBI 1000 Genomes Browser:

rs1554651403

Molecular consequence:

NR_003051.4:n.-20_-1dup - upstream transcript variant - [Sequence Ontology: SO:0001986]

Condition(s)

Name:: Anauxetic dysplasia
Synonyms:: SPONDYLOMETAEPIPHYSEAL DYSPLASIA, ANAUXETIC TYPE
Identifiers:: MONDO: MONDO:0011773; MedGen: C1846796; OMIM: PS607095

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50S ribosomal protein L24 [Tenacibaculum todarodis]
50S ribosomal protein L24 [Tenacibaculum todarodis]
gi|1110849588|gnl|PRJNA350758|LPB13 20|gb|APG63907.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001416874	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 18, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 32021596, 16244706, 12107819, 11207361, 16254002, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001416874

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 18, 2023)

germline

clinical testing

PubMed (6)
[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

Identification of Novel and Recurrent RMRP Variants in a Series of Brazilian Patients with Cartilage-Hair Hypoplasia: McKusick Syndrome.

Gomes ME, Calatrava Paternostro L, Moura VR, Antunes D, Caffarena ER, Horovitz D, Sanseverino MT, Ferraz Leal G, Felix TM, Pontes Cavalcanti D, Clinton Llerena J Jr, Gonzalez S.

Mol Syndromol. 2020 Jan;10(5):255-263. doi: 10.1159/000501892. Epub 2019 Aug 15.

PubMed [citation]

PMID:: 32021596
PMCID:: PMC6997793

Evolutionary comparison provides evidence for pathogenicity of RMRP mutations.

Bonafé L, Dermitzakis ET, Unger S, Greenberg CR, Campos-Xavier BA, Zankl A, Ucla C, Antonarakis SE, Superti-Furga A, Reymond A.

PLoS Genet. 2005 Oct;1(4):e47.

PubMed [citation]

PMID:: 16244706
PMCID:: PMC1262189

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001416874.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This variant occurs in the RMRP gene, which encodes an RNA molecule that does not result in a protein product. This variant is present in population databases (no rsID available, gnomAD 0.009%). This variant has been observed in individuals with cartilage-hair hypoplasia (PMID: 32021596). Other insertions and duplications immediately upstream of the coding sequence have been reported in individuals affected with cartilage-hair hypoplasia-anauxetic dysplasia (CHH-AD) spectrum disorders (PMID: 16244706, 11207361, 12107819). ClinVar contains an entry for this variant (Variation ID: 555121). While functional studies for this variant have not been reported, experimental analyses using patient derived cells, as well as in vitro transfection studies, have shown that promoter insertions result in silencing of RMRP transcription and reduced expression of the gene product (PMID: 11207361, 16254002). For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 13, 2024

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