NM_006295.3(VARS1):c.614_616del (p.Gly205del) AND Neurodevelopmental disorder with microcephaly, seizures, and cortical atrophy

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Aug 14, 2024
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:: RCV004720218.2

Allele description [Variation Report for NM_006295.3(VARS1):c.614_616del (p.Gly205del)]

NM_006295.3(VARS1):c.614_616del (p.Gly205del)

Genes:

LOC126859651:CDK7 strongly-dependent group 2 enhancer GRCh37_chr6:31759783-31760982 [Gene]
VARS1:valyl-tRNA synthetase 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

6p21.33

Genomic location:

Preferred name:

NM_006295.3(VARS1):c.614_616del (p.Gly205del)

HGVS:

NC_000006.12:g.31792804_31792806del
NG_028229.1:g.8132_8134del
NG_084152.1:g.899_901del
NM_006295.3:c.614_616delMANE SELECT
NP_006286.1:p.Gly205del
NC_000006.11:g.31760581_31760583del

Protein change:

G205del

Molecular consequence:

NM_006295.3:c.614_616del - inframe deletion - [Sequence Ontology: SO:0001822]

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
SCV005200501	Pediatrics, Sichuan Provincial Hospital For Women And Children	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 14, 2024)	maternal	reference population	PubMed (1) [See all records that cite this PMID]
SCV005416758	Juno Genomics, Hangzhou Juno Genomics, Inc	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005200501

Pediatrics, Sichuan Provincial Hospital For Women And Children

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 14, 2024)

maternal

reference population

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

SCV005416758

Juno Genomics, Hangzhou Juno Genomics, Inc

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

germline

clinical testing

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	maternal	yes	not provided	not provided	not provided	not provided	not provided	reference population

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 Pediatrics, Sichuan Provincial Hospital For Women And Children, SCV005200501.1

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

Description

The phenotype of this child is microcephaly and premature infantile epilepsy. ACGM: VARS1 variation c.614_616del was classified as likely pathogenic. PM2_Supporting+PM4+PM3+PP4. PM2_Supporting: This variant occurs very infrequently in the ExAC, gnomAD, Thousand-genome Asian population database. PM4: VARS1 gene variant c.614_616del is an inframe deletion mutation that results in a change in protein length. PM3: In this sample, another possible pathogenic variant, c.3203C>T, was detected at the trans position. PP4: The client's clinical symptoms were consistent with the dominant phenotype of NDMSCA.

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

From Juno Genomics, Hangzhou Juno Genomics, Inc, SCV005416758.1

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

Description

PM2_Supporting+PM4+PM3+PP4

#	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 30, 2024

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