SPTA1 A970D - GET-Evidence

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SPTA1 A970D

(SPTA1 Ala970Asp)


You are viewing an old version of this page that was saved on May 10, 2010 at 6:35pm by Madeleine Ball.

Short summary

This variant, also called α-IIa, has been seen frequently in individuals with recessive Hereditary pyropoikilocytosis. This appears to be the result of linkage to α-LEPRA (a C>T substitution at position -99 of intron 30); A970D is later reported as functionally neutral.

Variant evidence
Computational -
Functional
Case/Control
Familial
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

recessive

Summary of published research, and additional commentary

 

Allele frequency

  • T @ chr1:158624528: 3.7% (370/9916) in EVS
  • T @ chr1:156891151: 1.6% (2/128) in GET-Evidence
  • Frequency shown in summary reports: 3.7% (370/9916)

Publications
 

Maillet P, Alloisio N, Morlé L, Delaunay J. Spectrin mutations in hereditary elliptocytosis and hereditary spherocytosis. Hum Mutat. 1996;8(2):97-107. PubMed PMID: 8844207.

They mention the allele α-LEPRA as also implicated in hereditary spherocytosis, a C>T substitution at position -99 of intron 30. They say this is linked in cis to the α-IIs (A970D) substitution. The α-LEPRA variant appears to be implicated as the causal variant.

Edited in this revision:

Delaunay J, Nouyrigat V, Proust A, Schischmanoff PO, Cynober T, Yvart J, Gaillard C, Danos O, Tchernia G. Different impacts of alleles alphaLEPRA and alphaLELY as assessed versus a novel, virtually null allele of the SPTA1 gene in trans. Br J Haematol. 2004 Oct;127(1):118-22. PubMed PMID: 15384986.

This paper mentions A970D as a functionally neutral allele that is associated with α-LEPRA: “PCR screening of mutation αLEPRA and a functionally neutral mutation, Bughill (C→A, at position 11 of exon 21; GCT→GAT: A970D), which is inconstantly carried by allele αLEPRA”.

Costa DB, Lozovatsky L, Gallagher PG, Forget BG. A novel splicing mutation of the alpha-spectrin gene in the original hereditary pyropoikilocytosis kindred. Blood. 2005 Dec 15;106(13):4367-9. Epub 2005 Sep 8. PubMed PMID: 16150946; PubMed Central PMCID: PMC1895230.

This variant is noted to be linked to alpha-LEPRA and is seen frequently in individuals with recessive Hereditary pyropoikilocytosis.

Genomes
 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het T @ chr1:158624528

 

snp-18

 

Other external references
 

    dbSNP
  • rs35948326
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi

Other in silico analyses
 

  • NBLOSUM100 score = 5
  • GET-Evidence autoscore = 3

Edit history
 

Gene search

"GENE" or "GENE A123C":

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