NM_020320.5(RARS2):c.773G>A (p.Arg258His) AND Pontocerebellar hypoplasia type 6

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Mar 30, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000765897.9

Allele description [Variation Report for NM_020320.5(RARS2):c.773G>A (p.Arg258His)]

NM_020320.5(RARS2):c.773G>A (p.Arg258His)

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.773G>A (p.Arg258His)

HGVS:

NC_000006.12:g.87529647C>T
NG_008601.1:g.65371G>A
NM_001318785.2:c.248G>A
NM_001350505.2:c.773G>A
NM_001350506.2:c.248G>A
NM_001350507.2:c.248G>A
NM_001350508.2:c.248G>A
NM_001350509.2:c.248G>A
NM_001350510.2:c.248G>A
NM_001350511.2:c.248G>A
NM_020320.5:c.773G>AMANE SELECT
NP_001305714.1:p.Arg83His
NP_001337434.1:p.Arg258His
NP_001337435.1:p.Arg83His
NP_001337436.1:p.Arg83His
NP_001337437.1:p.Arg83His
NP_001337438.1:p.Arg83His
NP_001337439.1:p.Arg83His
NP_001337440.1:p.Arg83His
NP_064716.2:p.Arg258His
NC_000006.11:g.88239365C>T
NM_020320.3:c.773G>A
NR_134857.2:n.803G>A
NR_146738.2:n.1071G>A
NR_146739.2:n.884G>A
NR_146740.2:n.1148G>A
NR_146741.2:n.810G>A
NR_146742.2:n.1186G>A
NR_146743.2:n.1024G>A
NR_146744.2:n.1148G>A
NR_146745.2:n.807G>A
NR_146746.2:n.1242G>A
NR_146747.2:n.586G>A
NR_146748.2:n.1024G>A
NR_146749.2:n.1024G>A
NR_146750.2:n.1148G>A
NR_146751.2:n.1024G>A
NR_146752.2:n.1092G>A
NR_146753.2:n.940G>A
NR_146754.2:n.884G>A
NR_146755.2:n.1148G>A
NR_146756.2:n.803G>A
NR_146757.2:n.1074G>A
NR_146758.2:n.807G>A
NR_146759.2:n.807G>A

Protein change:

R258H

Links:

dbSNP: rs145297855

NCBI 1000 Genomes Browser:

rs145297855

Molecular consequence:

NM_001318785.2:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350505.2:c.773G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350506.2:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350507.2:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350508.2:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350509.2:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350510.2:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350511.2:c.248G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020320.5:c.773G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_134857.2:n.803G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146738.2:n.1071G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146739.2:n.884G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146740.2:n.1148G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146741.2:n.810G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146742.2:n.1186G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146743.2:n.1024G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146744.2:n.1148G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146745.2:n.807G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146746.2:n.1242G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146747.2:n.586G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146748.2:n.1024G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146749.2:n.1024G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146750.2:n.1148G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146751.2:n.1024G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146752.2:n.1092G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146753.2:n.940G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146754.2:n.884G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146755.2:n.1148G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146756.2:n.803G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146757.2:n.1074G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146758.2:n.807G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146759.2:n.807G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Pontocerebellar hypoplasia type 6 (PCH6)
Synonyms:: Encephalopathy fatal infantile with mitochondrial respiratory chain defects
Identifiers:: MONDO: MONDO:0012683; MedGen: C1969084; Orphanet: 166073; OMIM: 611523

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000897317	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 31, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002079904	Natera, Inc.	no assertion criteria provided	Uncertain significance (Jan 20, 2020)	germline	clinical testing
SCV004206131	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 30, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004244487	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 14, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

PMC

Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL.

Genetics in medicine : official journal of the American College of Medical Genetics. 2015 Mar 5; 17(5): 405-424

PMC [article]

PMCID:: PMC4544753
PMID:: 25741868
DOI:: 10.1038/gim.2015.30

Details of each submission

From Fulgent Genetics, Fulgent Genetics, SCV000897317.1

#	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

From Natera, Inc., SCV002079904.1

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004206131.2

#	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

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV004244487.1

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

Description

PM3_Strong, PM1

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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