NM_005859.5(PURA):c.671del (p.Ser223_Leu224insTer) AND PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 19, 2022
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:: RCV003749509.1

Allele description [Variation Report for NM_005859.5(PURA):c.671del (p.Ser223_Leu224insTer)]

NM_005859.5(PURA):c.671del (p.Ser223_Leu224insTer)

Gene:

PURA:purine rich element binding protein A [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q31.3

Genomic location:

Preferred name:

NM_005859.5(PURA):c.671del (p.Ser223_Leu224insTer)

HGVS:

NC_000005.10:g.140114852del
NG_041813.1:g.5730del
NG_105984.1:g.314del
NM_005859.5:c.671delMANE SELECT
NP_005850.1:p.Leu224Terfs
NP_005850.1:p.Ser223_Leu224insTer
NC_000005.9:g.139494436del
NC_000005.9:g.139494437del
NM_005859.4:c.671delT

Molecular consequence:

NM_005859.5:c.671del - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome (NEDRIHF)
Synonyms:: NEURODEVELOPMENTAL DISORDER WITH NEONATAL RESPIRATORY INSUFFICIENCY, HYPOTONIA, AND FEEDING DIFFICULTIES
Identifiers:: MedGen: C4015357; Orphanet: 438216; OMIM: 616158

Recent activity

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PREDICTED: Rattus norvegicus tyrosine kinase, non-receptor, 2 (Tnk2), transcript...
PREDICTED: Rattus norvegicus tyrosine kinase, non-receptor, 2 (Tnk2), transcript variant X22, mRNA
gi|2678884761|ref|XM_039088317.2|

Nucleotide
PREDICTED: Rattus norvegicus tyrosine kinase, non-receptor, 2 (Tnk2), transcript...
PREDICTED: Rattus norvegicus tyrosine kinase, non-receptor, 2 (Tnk2), transcript variant X24, mRNA
gi|2678884763|ref|XM_039088322.2|

Nucleotide
activated CDC42 kinase 1 [Rattus norvegicus]
activated CDC42 kinase 1 [Rattus norvegicus]
gi|56605750|ref|NP_001008337.1|

Protein
activated CDC42 kinase 1 isoform X13 [Rattus norvegicus]
activated CDC42 kinase 1 isoform X13 [Rattus norvegicus]
gi|2678884754|ref|XP_063126571.1|

Protein
PREDICTED: Rattus norvegicus tyrosine kinase, non-receptor, 2 (Tnk2), transcript...
PREDICTED: Rattus norvegicus tyrosine kinase, non-receptor, 2 (Tnk2), transcript variant X20, mRNA
gi|2678884760|ref|XM_039088316.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004412767	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 19, 2022)	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

SCV004412767

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 19, 2022)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV004412767.1

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

Description

This variant has not been reported in the literature in individuals affected with PURA-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the PURA protein in which other variant(s) (p.Thr310Asnfs*7 ) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu224*) in the PURA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 99 amino acid(s) of the PURA protein.

#	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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