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NM_020320.5(RARS2):c.1327T>C (p.Ser443Pro) AND Pontoneocerebellar hypoplasia

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jul 30, 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:
RCV002282147.1

Allele description [Variation Report for NM_020320.5(RARS2):c.1327T>C (p.Ser443Pro)]

NM_020320.5(RARS2):c.1327T>C (p.Ser443Pro)

Gene:
RARS2:arginyl-tRNA synthetase 2, mitochondrial [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6q15
Genomic location:
Preferred name:
NM_020320.5(RARS2):c.1327T>C (p.Ser443Pro)
HGVS:
  • NC_000006.12:g.87518718A>G
  • NG_008601.1:g.76300T>C
  • NM_001318785.2:c.802T>C
  • NM_001350505.2:c.1327T>C
  • NM_001350506.2:c.802T>C
  • NM_001350507.2:c.802T>C
  • NM_001350508.2:c.802T>C
  • NM_001350509.2:c.802T>C
  • NM_001350510.2:c.802T>C
  • NM_001350511.2:c.802T>C
  • NM_020320.5:c.1327T>CMANE SELECT
  • NP_001305714.1:p.Ser268Pro
  • NP_001337434.1:p.Ser443Pro
  • NP_001337435.1:p.Ser268Pro
  • NP_001337436.1:p.Ser268Pro
  • NP_001337437.1:p.Ser268Pro
  • NP_001337438.1:p.Ser268Pro
  • NP_001337439.1:p.Ser268Pro
  • NP_001337440.1:p.Ser268Pro
  • NP_064716.2:p.Ser443Pro
  • NC_000006.11:g.88228436A>G
  • NM_020320.3:c.1327T>C
  • NM_020320.4:c.1327T>C
  • NR_134857.2:n.1353T>C
  • NR_146738.2:n.1625T>C
  • NR_146739.2:n.1434T>C
  • NR_146740.2:n.1702T>C
  • NR_146741.2:n.1364T>C
  • NR_146742.2:n.1736T>C
  • NR_146743.2:n.1574T>C
  • NR_146744.2:n.1702T>C
  • NR_146745.2:n.1361T>C
  • NR_146746.2:n.1796T>C
  • NR_146747.2:n.1140T>C
  • NR_146748.2:n.1600T>C
  • NR_146749.2:n.1574T>C
  • NR_146750.2:n.1698T>C
  • NR_146751.2:n.1578T>C
  • NR_146752.2:n.1642T>C
  • NR_146753.2:n.1494T>C
  • NR_146754.2:n.1438T>C
  • NR_146755.2:n.1702T>C
  • NR_146756.2:n.1357T>C
  • NR_146757.2:n.1628T>C
  • NR_146758.2:n.1357T>C
  • NR_146759.2:n.1357T>C
Protein change:
S268P
Links:
dbSNP: rs775295739
NCBI 1000 Genomes Browser:
rs775295739
Molecular consequence:
  • NM_001318785.2:c.802T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350505.2:c.1327T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350506.2:c.802T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350507.2:c.802T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350508.2:c.802T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350509.2:c.802T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350510.2:c.802T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350511.2:c.802T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020320.5:c.1327T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_134857.2:n.1353T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146738.2:n.1625T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146739.2:n.1434T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146740.2:n.1702T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146741.2:n.1364T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146742.2:n.1736T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146743.2:n.1574T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146744.2:n.1702T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146745.2:n.1361T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146746.2:n.1796T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146747.2:n.1140T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146748.2:n.1600T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146749.2:n.1574T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146750.2:n.1698T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146751.2:n.1578T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146752.2:n.1642T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146753.2:n.1494T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146754.2:n.1438T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146755.2:n.1702T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146756.2:n.1357T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146757.2:n.1628T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146758.2:n.1357T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146759.2:n.1357T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Pontoneocerebellar hypoplasia
Synonyms:
Pontocerebellar hypoplasia; Non-syndromic pontocerebellar hypoplasia
Identifiers:
MONDO: MONDO:0020135; MedGen: C1261175; Orphanet: 98523; OMIM: PS607596

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002570914Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Jul 30, 2022) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

New genes and pathomechanisms in mitochondrial disorders unraveled by NGS technologies.

Legati A, Reyes A, Nasca A, Invernizzi F, Lamantea E, Tiranti V, Garavaglia B, Lamperti C, Ardissone A, Moroni I, Robinson A, Ghezzi D, Zeviani M.

Biochim Biophys Acta. 2016 Aug;1857(8):1326-1335. doi: 10.1016/j.bbabio.2016.02.022. Epub 2016 Mar 8.

PubMed [citation]
PMID:
26968897

Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease.

Karaca E, Harel T, Pehlivan D, Jhangiani SN, Gambin T, Coban Akdemir Z, Gonzaga-Jauregui C, Erdin S, Bayram Y, Campbell IM, Hunter JV, Atik MM, Van Esch H, Yuan B, Wiszniewski W, Isikay S, Yesil G, Yuregir OO, Tug Bozdogan S, Aslan H, Aydin H, Tos T, et al.

Neuron. 2015 Nov 4;88(3):499-513. doi: 10.1016/j.neuron.2015.09.048.

PubMed [citation]
PMID:
26539891
PMCID:
PMC4824012
See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002570914.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

Variant summary: RARS2 c.1327T>C (p.Ser443Pro) results in a non-conservative amino acid change located in the Arginyl-tRNA synthetase, catalytic core domain (IPR035684) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 251374 control chromosomes. c.1327T>C has been reported in the literature as homozygous and compound heterozygous genotype in individuals reportedly affected with features of infantile-onset myoclonic developmental and epleptic encephalopathy/Neurogenetic disorders with brain malfornations/mitochondorial disorders/a neuroradiological diagnosis of Pontocerebellar Hypoplasia (PCH) (example, Karaca_2015, Legati_2016, Matricardi_2019, Nuovo_2022, de Valles-lanez_2022). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024