Fetal anomalies
Gene: ACVRL1

ACVRL1 (activin A receptor like type 1)
EnsemblGeneIds (GRCh38): ENSG00000139567
EnsemblGeneIds (GRCh37): ENSG00000139567
OMIM: 601284, Gene2Phenotype
ACVRL1 is in 9 panels

5 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance updated to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted following NHS Genomic Medicine Service approval.
Created: 26 Sep 2024, 11:09 a.m. | Last Modified: 26 Sep 2024, 11:09 a.m.

Panel Version: 4.192

This gene and phenotype were reviewed during meetings between November 2023 & July 2024. The meetings included representatives of the North Thames and Central & South R21 testing GLHs and from the R21 Clinical Oversight Group. Clinical review and curation was performed by Natalie Chandler, Alison Male and Lyn Chitty (North Thames GLH), Stephanie Allen, Natalie Bibb, Esther Kinning and Denise Williams (Central & South GLH) and Natalie Canham, Anna De Burca and Samantha Doyle R21 Clinical Oversight Group. Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Created: 29 Aug 2024, 8:33 p.m. | Last Modified: 29 Aug 2024, 8:33 p.m.

Panel Version: 4.36

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Created: 29 Aug 2024, 8:33 p.m.
Last Modified: 29 Aug 2024, 8:33 p.m.
Panel version: 4.192

Stephanie Allen (Birmingham Women's NHS Foundation Trust)

Green List (high evidence)

There is some published evidence for prenatal phenotype with ACVRL1 (albeit rare): PMID:27381467 - 2 cases with hepatic AVMs and resultant cardiomegaly detected prenatally (in both cases they had specialist scanning in pregnancy because of previous neonatal death with hepatic AVM). PMID:32170914 - a 2020 case report of ACVRL1 presenting as vein of galen malformation in a fetus PMID:37668039 - Heart failure caused by congenital hepatic hemangioma complicated with arteriovenous fistula in a neonate. Prenatal ultrasound suggested abnormal development of the fetal liver vessels. If we think VOGM could be detected prenatally then yes include. Green.
Created: 29 Aug 2024, 8:07 p.m. | Last Modified: 29 Aug 2024, 8:07 p.m.

Panel Version: 4.35

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Telangiectasia, hereditary hemorrhagic, type 2, OMIM:600376

Publications

Created: 29 Aug 2024, 8:07 p.m.
Last Modified: 29 Aug 2024, 8:07 p.m.
Panel version: 4.35

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Updated rating from Red to Amber inline with this recent Amber review by Rhiannon Mellis (GOSH), awaiting further evidence supporting that this gene can cause a fetal phenotype.
Created: 19 Aug 2022, 10:23 a.m. | Last Modified: 19 Aug 2022, 10:23 a.m.

Panel Version: 1.906

Created: 19 Aug 2022, 10:23 a.m.
Last Modified: 19 Aug 2022, 10:23 a.m.
Panel version: 1.906

Rhiannon Mellis (Great Ormond Street Hospital)

I don't know

This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.

Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).

Outcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene.

Details of review:
Consistency check because out of 4 known HHT genes EPHB4 and SMAD4 are on the fetal anomalies panel but ACVRL1 and ENG are not.

There is some published evidence for prenatal phenotype with ACVRL1 (albeit rare): PMID: 27381467 = 2 cases with hepatic AVMs and resultant cardiomegaly detected prenatally (in both cases they had specialist scanning in pregnancy because of previous neonatal death with hepatic AVM). And PMID: 32170914 = a 2020 case report of ACVRL1 presenting as vein of galen malformation in a fetus (pathogenic variant also confirmed in other affected family members).
Created: 11 Aug 2022, 2:05 p.m. | Last Modified: 11 Aug 2022, 2:05 p.m.

Panel Version: 1.900

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Telangiectasia, hereditary hemorrhagic, type 2

Publications

PMID: 27381467
32170914

Created: 11 Aug 2022, 2:05 p.m.
Last Modified: 11 Aug 2022, 2:05 p.m.
Panel version: 1.900

Rebecca Foulger (Genomics England curator)

I don't know

DDG2P rating in original PAGE list: Possible.
Created: 11 Dec 2018, 9:04 a.m.

Created: 11 Dec 2018, 9:04 a.m.

Panel version: 0.9

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
NHS GMS
PAGE Additional Gene List

Phenotypes

Telangiectasia, hereditary hemorrhagic, type 2, OMIM:600376

OMIM

601284

Clinvar variants

Variants in ACVRL1

Penetrance

None

Publications

Panels with this gene