NM_001673.5(ASNS):c.1649G>A (p.Arg550His) AND Congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome - ClinVar

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NM_001673.5(ASNS):c.1649G>A (p.Arg550His) AND Congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Nov 15, 2018
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000984516.5

Allele description

NM_001673.5(ASNS):c.1649G>A (p.Arg550His)

Genes:

CZ1P-ASNS:CZ1P-ASNS readthrough [Gene]
ASNS:asparagine synthetase (glutamine-hydrolyzing) [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q21.3

Genomic location:

Preferred name:

NM_001673.5(ASNS):c.1649G>A (p.Arg550His)

HGVS:

NC_000007.14:g.97852296C>T
NG_033870.2:g.81267G>A
NM_001178075.2:c.1586G>A
NM_001178076.2:c.1400G>A
NM_001178077.1:c.1400G>A
NM_001352496.2:c.1649G>A
NM_001673.5:c.1649G>AMANE SELECT
NM_133436.3:c.1649G>A
NM_183356.4:c.1649G>A
NP_001171546.1:p.Arg529His
NP_001171547.1:p.Arg467His
NP_001171548.1:p.Arg467His
NP_001339425.1:p.Arg550His
NP_001664.3:p.Arg550His
NP_597680.2:p.Arg550His
NP_899199.2:p.Arg550His
NP_899199.2:p.Arg550His
NC_000007.13:g.97481608C>T
NC_000007.13:g.97481608C>T
NM_001673.4:c.1649G>A
NM_183356.3:c.1649G>A
NR_147989.1:n.3352G>A
p.Arg550His

Protein change:

R467H

Links:

dbSNP: rs552452349

NCBI 1000 Genomes Browser:

rs552452349

Molecular consequence:

NM_001178075.2:c.1586G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001178076.2:c.1400G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001178077.1:c.1400G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001352496.2:c.1649G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001673.5:c.1649G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133436.3:c.1649G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_183356.4:c.1649G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_147989.1:n.3352G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome
Synonyms:: ASNS DEFICIENCY; Asparagine synthetase deficiency
Identifiers:: MONDO: MONDO:0014258; MedGen: C3809971; Orphanet: 391376; OMIM: 615574

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Fusarium sp. f37 CM-2013 28S ribosomal RNA gene, partial sequence
Fusarium sp. f37 CM-2013 28S ribosomal RNA gene, partial sequence
gi|574453613|gb|KF733380.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001132573	Broad Institute Rare Disease Group, Broad Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 15, 2018)	germline	research	PubMed (2) [See all records that cite these PMIDs] 29405484, 25741868
SCV002053928	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]
SCV002079400	Natera, Inc.	no assertion criteria provided	Likely pathogenic (Oct 23, 2020)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001132573

Broad Institute Rare Disease Group, Broad Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 15, 2018)

germline

research

PubMed (2)
[See all records that cite these PMIDs]

SCV002053928

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]

SCV002079400

Natera, Inc.

no assertion criteria provided

Likely pathogenic
(Oct 23, 2020)

germline

clinical testing

Help

Summary from all submissions

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

Citations

PubMed

Report of four novel variants in ASNS causing asparagine synthetase deficiency and review of literature.

Galada C, Hebbar M, Lewis L, Soans S, Kadavigere R, Srivastava A, Bielas S, Girisha KM, Shukla A.

Congenit Anom (Kyoto). 2018 Sep;58(5):181-182. doi: 10.1111/cga.12275. Epub 2018 Feb 20. Review. No abstract available.

PubMed [citation]

PMID:: 29405484
PMCID:: PMC6338226

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 Institute Rare Disease Group, Broad Institute, SCV001132573.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (2)

Description

The homozygous p.Arg550His variant in ASNS was identified by our study in one individual with Asparagine Synthetase Deficiency. This variant has been identified in the literature in the case of one homozygous affected proband (Galada et al. 2018; PMID: 29405484). Another homozygous affected proband was reported in the literature (Faoucher et al. 2017). This variant has been identified in <0.01% (2/24030) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs552452349). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic.

#	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

From Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India, SCV002053928.1

#	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

From Natera, Inc., SCV002079400.1

#	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

Last Updated: Feb 28, 2024

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