Congenital muscular dystrophy
Gene: HNRNPA2B1
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 4:51 p.m. | Last Modified: 1 Feb 2023, 4:51 p.m.
Panel Version: 3.22
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.Created: 15 Dec 2022, 12:02 p.m. | Last Modified: 15 Dec 2022, 12:02 p.m.
Panel Version: 3.11
Comment on phenotypes: The OMIM phenotype for HNRNPA2B1 (?Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2, OMIM:615422) is based on one family. PMID: 35484142 presents further variants associated with an expanded phenotype.Created: 15 Dec 2022, 12:01 p.m. | Last Modified: 15 Dec 2022, 12:01 p.m.
Panel Version: 3.10
PMID: 35484142 reports nine heterozygous terminating HNRNPA2B1 variants in ten unrelated cases of early onset severe, progressive muscular dystrophy, reminiscent of oculopharyngeal muscular dystrophy (OPMD)Created: 15 Dec 2022, 11:57 a.m. | Last Modified: 15 Dec 2022, 11:57 a.m.
Panel Version: 3.9
The Q1_22_rating tag has been added as the GMS review for this gene has not been received to dateCreated: 3 Feb 2022, 4:16 p.m. | Last Modified: 3 Feb 2022, 4:16 p.m.
Panel Version: 2.21
Comment on list classification: De novo terminating variants clustered in the C-terminus of the protein have been reported in six unrelated families all with a distinct class of dominantly-acting heterozygous variants in hnRNPA2B1 with a unique clinical phenotype of early childhood-onset progressive muscle weakness, ophthalmoplegia, ptosis, dysphagia, and variable degrees of respiratory insufficiency but no dementia (https://www.nmd-journal.com/article/S0960-8966(20)30203-0/fulltext).
This source is a meeting abstract an there is no peer reviewed source at this time.
There is enough evidence for this gene to be green, but GMS opinion is required to confirm this.Created: 12 Jan 2021, 3:02 p.m. | Last Modified: 28 Jan 2021, 5:54 p.m.
Panel Version: 2.5
Phenotypes
early-onset oculopharyngeal muscular dystrophy
Publications
ten independent families reported with a severe, progressive muscular dystrophy with early onset, and de novo frameshift variants in this gene. phenotype is caractherised by symptoms onset before 2 years of age with severe respiratory insufficiency, delayed motor milestones, ptosis and ophthalmoplegia, axial weakness, progressive proximal and distal weakness. Creatine kinase levels were elevated. Disease-causing frameshift mutations abolish the native stop codon and extend the reading frame, creating novel transcripts that escape nonsense-mediated decay and alter the nucleocytoplasmic transport dynamics. in view of this evidence this gene should be upgraded to greenCreated: 10 Nov 2022, 12:35 p.m. | Last Modified: 10 Nov 2022, 12:35 p.m.
Panel Version: 2.31
de novo variants in this gene have been reported in multiple unrelated families and presented at the World muscle society congress 2020, a full publication is currently in progress. see abstract:
https://www.nmd-journal.com/article/S0960-8966(20)30203-0/fulltext
Sources: Other, Expert list, ResearchCreated: 8 Dec 2020, 2:21 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
early-onset oculopharyngeal muscular dystrophy, muscular dystrophy, congenital myopathy
Publications
Phenotypes for gene: HNRNPA2B1 were changed from early-onset oculopharyngeal muscular dystrophy, muscular dystrophy, congenital myopathy to Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2, OMIM:615422
Tag watchlist was removed from gene: HNRNPA2B1.
Tag for-review was removed from gene: HNRNPA2B1. Tag Q1_22_rating was removed from gene: HNRNPA2B1. Tag Q4_22_promote_green was removed from gene: HNRNPA2B1.
Source Expert Review Green was added to HNRNPA2B1. Source NHS GMS was added to HNRNPA2B1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q4_22_promote_green tag was added to gene: HNRNPA2B1.
Gene: hnrnpa2b1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: HNRNPA2B1 were changed from ?Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2, OMIM:615422; inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2, MONDO:0014178 to early-onset oculopharyngeal muscular dystrophy, muscular dystrophy, congenital myopathy
Phenotypes for gene: HNRNPA2B1 were changed from oculopharyngodistal myopathy, muscular dystrophy, congenital myopathy to ?Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2, OMIM:615422; inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2, MONDO:0014178
Publications for gene: HNRNPA2B1 were set to https://www.nmd-journal.com/article/S0960-8966(20)30203-0/fulltext
Tag Q1_22_rating tag was added to gene: HNRNPA2B1.
Tag watchlist tag was added to gene: HNRNPA2B1. Tag for-review tag was added to gene: HNRNPA2B1.
Publications for gene: HNRNPA2B1 were set to
Gene: hnrnpa2b1 has been classified as Amber List (Moderate Evidence).
gene: HNRNPA2B1 was added gene: HNRNPA2B1 was added to Congenital muscular dystrophy. Sources: Other,Expert list,Research Mode of inheritance for gene: HNRNPA2B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: HNRNPA2B1 were set to oculopharyngodistal myopathy, muscular dystrophy, congenital myopathy Review for gene: HNRNPA2B1 was set to GREEN