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Severe microcephaly

Gene: AP4S1

Amber List (moderate evidence)

AP4S1 (adaptor related protein complex 4 sigma 1 subunit)
EnsemblGeneIds (GRCh38): ENSG00000100478
EnsemblGeneIds (GRCh37): ENSG00000100478
OMIM: 607243, Gene2Phenotype
AP4S1 is in 9 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark. Rating Amber with recommendation of review by the GMS team to assess whether there is sufficient evidence to support a Green rating (added 'for-review' tag)
Created: 27 Jan 2021, 4:59 p.m. | Last Modified: 27 Jan 2021, 4:59 p.m.
Panel Version: 2.88
Literature search revealed at least 23 individuals from 17 unrelated families reported in literature with biallelic variants in this gene (PMID: 21620353; 25552650; 27444738; 30283821; 32216065; 32979048). Microcephaly was observed in 15/21 cases but precise details regarding head circumference were mostly omitted or presentation was too mild relative to the scope of this panel. However, at least 2 individuals (2 families) did have microcephaly of relevant severity (OFC ≤ -3 SD) (see PMIDs: 21620353 and 25552650).

This disorder may be better represented by other panels (e.g. HSP, ID) for which this gene is already Green.

- PMID: 32216065 (2020) - Zebrafish model recapitulates several human phenotypes, including decreased head size.
Created: 27 Jan 2021, 4:58 p.m. | Last Modified: 27 Jan 2021, 5:02 p.m.
Panel Version: 2.88

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Borderline Amber/Green as only one affected individual <-3SD; however, part of same gene family as other spastic paraplegias with microcephaly. Microcephaly in another family -2SD and precise information on the microcephaly not available for third family.
Sources: Expert list
Created: 31 Aug 2020, 11:06 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic paraplegia 52, autosomal recessive (MIM#614067)

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Spastic paraplegia 52, autosomal recessive, OMIM:614067
  • Hereditary spastic paraplegia 52, MONDO:0013552
Tags
for-review
OMIM
607243
Clinvar variants
Variants in AP4S1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

27 Jan 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: AP4S1 were changed from Spastic paraplegia 52, autosomal recessive (MIM#614067) to Spastic paraplegia 52, autosomal recessive, OMIM:614067; Hereditary spastic paraplegia 52, MONDO:0013552

27 Jan 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: ap4s1 has been classified as Amber List (Moderate Evidence).

27 Jan 2021, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: AP4S1.

31 Aug 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Zornitza Stark (Australian Genomics)

gene: AP4S1 was added gene: AP4S1 was added to Severe microcephaly. Sources: Expert list Mode of inheritance for gene: AP4S1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AP4S1 were set to 21620353; 25552650; 27444738 Phenotypes for gene: AP4S1 were set to Spastic paraplegia 52, autosomal recessive (MIM#614067) Review for gene: AP4S1 was set to GREEN gene: AP4S1 was marked as current diagnostic