NM_006295.3(VARS1):c.2590_2592delinsTGA (p.Ser864Ter) AND Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jul 10, 2023
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV003493393.1

Allele description [Variation Report for NM_006295.3(VARS1):c.2590_2592delinsTGA (p.Ser864Ter)]

NM_006295.3(VARS1):c.2590_2592delinsTGA (p.Ser864Ter)

Gene:

VARS1:valyl-tRNA synthetase 1 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

6p21.33

Genomic location:

Preferred name:

NM_006295.3(VARS1):c.2590_2592delinsTGA (p.Ser864Ter)

Other names:

p.S864*

HGVS:

NC_000006.12:g.31781076_31781078delinsTCA
NG_028229.1:g.19858_19860delinsTGA
NM_006295.3:c.2590_2592delinsTGAMANE SELECT
NP_006286.1:p.Ser864Ter
NC_000006.11:g.31748853_31748855delinsTCA

Protein change:

S864*

Molecular consequence:

NM_006295.3:c.2590_2592delinsTGA - nonsense - [Sequence Ontology: SO:0001587]

Functional consequence:

NMD_triggering_variant [Sequence Ontology: SO:0002319] - Comment(s)

Observations:

Condition(s)

Name:: Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy
Identifiers:: MONDO: MONDO:0060621; MedGen: C4540493; OMIM: 617802

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004242223	Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN	no assertion criteria provided	Likely pathogenic (Jul 10, 2023)	maternal	clinical testing, research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004242223

Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN

no assertion criteria provided

Likely pathogenic
(Jul 10, 2023)

maternal

clinical testing, 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	maternal	yes	1	not provided	not provided	not provided	not provided	clinical testing, research

Citations

PubMed

Transcriptome-directed analysis for Mendelian disease diagnosis overcomes limitations of conventional genomic testing.

Murdock DR, Dai H, Burrage LC, Rosenfeld JA, Ketkar S, Müller MF, Yépez VA, Gagneur J, Liu P, Chen S, Jain M, Zapata G, Bacino CA, Chao HT, Moretti P, Craigen WJ, Hanchard NA; Undiagnosed Diseases Network, Lee B.

J Clin Invest. 2021 Jan 4;131(1). doi:pii: 141500. 10.1172/JCI141500.

PubMed [citation]

PMID:: 33001864
PMCID:: PMC7773386

Details of each submission

From Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN, SCV004242223.1

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

Description

RNAseq showed decreased level of expression with skewing to the alternate allele, supporting NMD

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

Last Updated: Feb 14, 2024

ClinVar

Relating variation to medicine