NM_006303.4(AIMP2):c.105C>A (p.Tyr35Ter) AND Leukodystrophy, hypomyelinating, 17

Germline classification:: Likely pathogenic (2 submissions)
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:: RCV000656387.3

Allele description [Variation Report for NM_006303.4(AIMP2):c.105C>A (p.Tyr35Ter)]

NM_006303.4(AIMP2):c.105C>A (p.Tyr35Ter)

Gene:

AIMP2:aminoacyl tRNA synthetase complex interacting multifunctional protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p22.1

Genomic location:

Preferred name:

NM_006303.4(AIMP2):c.105C>A (p.Tyr35Ter)

HGVS:

NC_000007.14:g.6009468C>A
NG_008466.1:g.4639G>T
NG_050738.1:g.5218C>A
NM_001326606.2:c.15+90C>A
NM_001326607.2:c.105C>A
NM_001326609.2:c.-216C>A
NM_001326610.2:c.-251+90C>A
NM_001326611.3:c.-238+90C>A
NM_006303.4:c.105C>AMANE SELECT
NP_001313536.1:p.Tyr35Ter
NP_006294.2:p.Tyr35Ter
LRG_161:g.4639G>T
NC_000007.13:g.6049099C>A
NM_006303.3:c.105C>A

Protein change:

Y35*; TYR35TER

Links:

OMIM: 600859.0001; dbSNP: rs529613640

NCBI 1000 Genomes Browser:

rs529613640

Molecular consequence:

NM_001326609.2:c.-216C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001326606.2:c.15+90C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001326610.2:c.-251+90C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001326611.3:c.-238+90C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001326607.2:c.105C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_006303.4:c.105C>A - nonsense - [Sequence Ontology: SO:0001587]

Functional consequence:

protein truncation [Variation Ontology: 0015]

Condition(s)

Name:: Leukodystrophy, hypomyelinating, 17
Identifiers:: MONDO: MONDO:0054817; MedGen: C4693912; OMIM: 618006

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000778393	OMIM	no assertion criteria provided	Pathogenic (Jun 5, 2018)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002053931	Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	inherited	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000778393

OMIM

no assertion criteria provided

Pathogenic
(Jun 5, 2018)

germline

literature only

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

SCV002053931

Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

inherited

research

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	inherited	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Homozygosity for a nonsense variant in AIMP2 is associated with a progressive neurodevelopmental disorder with microcephaly, seizures, and spastic quadriparesis.

Shukla A, Das Bhowmik A, Hebbar M, Rajagopal KV, Girisha KM, Gupta N, Dalal A.

J Hum Genet. 2018 Jan;63(1):19-25. doi: 10.1038/s10038-017-0363-1. Epub 2017 Nov 16.

PubMed [citation]

PMID:: 29215095

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 OMIM, SCV000778393.1

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

Description

In 4 patients from 2 unrelated consanguineous families of Indian descent with hypomyelinating leukodystrophy-17 (HLD17; 618006), Shukla et al. (2018) identified a homozygous c.105C-A transversion (c.105C-A, NM_006303.3) in exon 1 of the AIMP2 gene, resulting in a tyr35-to-ter (Y35X) substitution. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in both families. The variant was not found in the homozygous state in the 1000 Genomes Project, Exome Variant Server, ExAC database, or in an in-house database of local individuals. It was found in the heterozygous state at a very low frequency in the gnomAD database (1 in 227,386). The variant was in a common region of homozygosity in the families, suggesting a founder effect. Patient cells showed mildly decreased AIMP2 mRNA compared to controls, although the difference was not statistically significant. Additional functional studies were not performed.

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

From Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India, SCV002053931.1

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

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

Last Updated: Feb 25, 2023

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