Intellectual disability
Gene: FRYL

FRYL (FRY like transcription coactivator)
EnsemblGeneIds (GRCh38): ENSG00000075539
EnsemblGeneIds (GRCh37): ENSG00000075539
FRYL is in 3 panels

1 review

Arina Puzriakova (Genomics England Curator)

I don't know

Comment on list classification: Rating Amber as overall the evidence is borderline. Only one recent study (PMID:38479391) has reported an disease association for FRYL, with variable phenotypes and results from functional studies, as well as variants in other genes in several cases. Additional studies are required to conclusively corroborate causality (added watchlist tag).
Created: 15 Apr 2024, 3:41 p.m. | Last Modified: 15 Apr 2024, 3:41 p.m.

Panel Version: 5.523

New association linking this gene to disease which is not yet listed in OMIM or Gene2Phenotype. There are no sequence variants in Decipher and ClinVar shows only a single pathogenic frameshift variant (c.1224del, p.Lys409fs) for FRYL-associated neurodevelopmental disorder, amongst multiple SNVs which are mostly missense VUS or B/LB.

Pan et al., 2024 (PMID: 38479391) reported 14 individuals with heterozygous variant in FRYL who presented with DD/ID, dysmorphic features, and other congenital anomalies in multiple systems. Except for DD/ID which was the only universal feature, observed phenotypes were variable and nonspecific.

Variants were confirmed de novo in all except one individual (duo testing excluded paternal inheritance although it was present at low frequency in gnomAD). Variant types include missense (5), fs/stop-gain (8) and canonical splice (1). Modelling 4/5 patient missense variants using flies showed that only one serves as a severe LoF variant, two others behave as partial LoF variants, and one variant had no functional impact (only variant not confirmed as de novo indicating this is a VUS). Four individuals also had P/LP variants in other genes (SF3B4, DHCR7, SLC6A19, SDHA) which could at least partially explain their phenotypes, and a further four harboured additional VUSs.
Sources: Literature
Created: 15 Apr 2024, 3:34 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder, MONDO:0700092

Publications

38479391

Created: 15 Apr 2024, 3:34 p.m.

Panel version: 5.522

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Amber
Literature

Phenotypes

Neurodevelopmental disorder, MONDO:0700092

Tags

watchlist

Clinvar variants

Variants in FRYL

Penetrance

None

Publications

38479391

Panels with this gene

History Filter Activity

15 Apr 2024, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

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

15 Apr 2024, Gel status: 1

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

Arina Puzriakova (Genomics England Curator)

gene: FRYL was added gene: FRYL was added to Intellectual disability - microarray and sequencing. Sources: Literature watchlist tags were added to gene: FRYL. Mode of inheritance for gene: FRYL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FRYL were set to 38479391 Phenotypes for gene: FRYL were set to Neurodevelopmental disorder, MONDO:0700092 Review for gene: FRYL was set to AMBER

Intellectual disability Gene: FRYL