NM_005859.5(PURA):c.148del (p.Ala50fs) AND PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 3, 2019
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:: RCV001239908.8

Allele description [Variation Report for NM_005859.5(PURA):c.148del (p.Ala50fs)]

NM_005859.5(PURA):c.148del (p.Ala50fs)

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.148del (p.Ala50fs)

HGVS:

NC_000005.10:g.140114329del
NG_041813.1:g.5207del
NM_005859.5:c.148delMANE SELECT
NP_005850.1:p.Ala50fs
NC_000005.9:g.139493911del
NC_000005.9:g.139493914del
NM_005859.4:c.148del

Protein change:

A50fs

Links:

dbSNP: rs1554129035

NCBI 1000 Genomes Browser:

rs1554129035

Molecular consequence:

NM_005859.5:c.148del - frameshift variant - [Sequence Ontology: SO:0001589]

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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NBB2001-086
NBB2001-086

biosample
LCP family protein [Streptococcus salivarius]
LCP family protein [Streptococcus salivarius]
gi|2575279551|ref|WP_309164731.1|

Protein
Pathogen: clinical or host-associated sample from Streptococcus agalactiae
Pathogen: clinical or host-associated sample from Streptococcus agalactiae

biosample
Streptococcus agalactiae strain ES-PW-088, whole genome shotgun sequencing proje...
Streptococcus agalactiae strain ES-PW-088, whole genome shotgun sequencing project
gi|825830330|gb|LCVN00000000.1|LCVN 000

Nucleotide
Streptococcus agalactiae strain SH2898, whole genome shotgun sequencing project
Streptococcus agalactiae strain SH2898, whole genome shotgun sequencing project
gi|825923417|gb|LDAL00000000.1|LDAL 000

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001412811	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 3, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25439098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001412811

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 3, 2019)

germline

clinical testing

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

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

Mutations in PURA cause profound neonatal hypotonia, seizures, and encephalopathy in 5q31.3 microdeletion syndrome.

Lalani SR, Zhang J, Schaaf CP, Brown CW, Magoulas P, Tsai AC, El-Gharbawy A, Wierenga KJ, Bartholomew D, Fong CT, Barbaro-Dieber T, Kukolich MK, Burrage LC, Austin E, Keller K, Pastore M, Fernandez F, Lotze T, Wilfong A, Purcarin G, Zhu W, Craigen WJ, et al.

Am J Hum Genet. 2014 Nov 6;95(5):579-83. doi: 10.1016/j.ajhg.2014.09.014. Epub 2014 Oct 16.

PubMed [citation]

PMID:: 25439098
PMCID:: PMC4225583

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001412811.5

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the PURA protein. Other variant(s) that disrupt this region (p.Gln186*, p.Tyr261*) have been determined to be pathogenic (PMID: 25439098). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with PURA-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change results in a premature translational stop signal in the PURA gene (p.Ala50Profs*28). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 273 amino acids 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: Sep 29, 2024

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