NM_002161.6(IARS1):c.2229+5G>A AND Growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 2, 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:: RCV003226048.2

Allele description [Variation Report for NM_002161.6(IARS1):c.2229+5G>A]

NM_002161.6(IARS1):c.2229+5G>A

Gene:

IARS1:isoleucyl-tRNA synthetase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.31

Genomic location:

Preferred name:

NM_002161.6(IARS1):c.2229+5G>A

Other names:

NM_001378586.1:c.2229+5G>A

HGVS:

NC_000009.12:g.92253357C>T
NG_051498.1:g.45400G>A
NM_001374299.1:c.2229+5G>A
NM_001374300.1:c.2229+5G>A
NM_001374301.1:c.2145+5G>A
NM_001378569.1:c.2292+5G>A
NM_001378571.1:c.2250+5G>A
NM_001378572.1:c.2229+5G>A
NM_001378573.1:c.2229+5G>A
NM_001378574.1:c.2229+5G>A
NM_001378575.1:c.2229+5G>A
NM_001378576.1:c.2229+5G>A
NM_001378577.1:c.2229+5G>A
NM_001378578.1:c.2229+5G>A
NM_001378579.1:c.2229+5G>A
NM_001378580.1:c.2229+5G>A
NM_001378582.1:c.2134-1472G>A
NM_001378583.1:c.2106+5G>A
NM_001378584.1:c.2229+5G>A
NM_001378585.1:c.2229+5G>A
NM_001378586.1:c.2229+5G>A
NM_002161.6:c.2229+5G>AMANE SELECT
NM_013417.4:c.2229+5G>A
NC_000009.11:g.95015639C>T

Molecular consequence:

NM_001374299.1:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001374300.1:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001374301.1:c.2145+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378569.1:c.2292+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378571.1:c.2250+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378572.1:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378573.1:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378574.1:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378575.1:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378576.1:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378577.1:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378578.1:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378579.1:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378580.1:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378582.1:c.2134-1472G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378583.1:c.2106+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378584.1:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378585.1:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001378586.1:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_002161.6:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_013417.4:c.2229+5G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy (GRIDHH)
Synonyms:: GROWTH RETARDATION, IMPAIRED INTELLECTUAL DEVELOPMENT, HYPOTONIA, AND HEPATOPATHY
Identifiers:: MONDO: MONDO:0014911; MedGen: C4310720; OMIM: 617093

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Nucleotide
txid170679[orgn] AND "strain 38 P 215"[All Fields] (56)
Nucleotide
Gene Links for Nucleotide (Select 954183661) (1)
Gene
ub3 [Zea mays]
ub3 [Zea mays]
Gene ID:103654498

Gene
GSE212633[Accession] (6)
GEO DataSets

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003922140	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 2, 2023)	germline	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003922140

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 2, 2023)

germline

curation

PubMed (1)
[See all records that cite this PMID]

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	curation

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

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV003922140.1

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

Description

The heterozygous c.2229+5G>A variant in IARS was identified by our study, in the compound heterozygous state along with another variant of uncertain significance (dbSNP ID: rs149536604), in two siblings with microcephaly, seizures, structural brain anomalies, and intellectual disability. These individuals also carried another variant of uncertain significance (dbSNP ID: rs149536604), however the phase of these variants are unknown at this time. The c.2229+5G>A variant in IARS has not been previously reported in individuals with growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy. This variant was absent from large population studies. This variant is located in the 5' splice region. Computational tools predict a splicing impact, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the c.2229+5G>A variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting, PP3 (Richards 2015).

#	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: Mar 30, 2024

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