Genes in panel
STRs in panel
Prev Next
Regions in panel
Prev Next

Arthrogryposis

Gene: BICD2

Green List (high evidence)

BICD2 (BICD cargo adaptor 2)
EnsemblGeneIds (GRCh38): ENSG00000185963
EnsemblGeneIds (GRCh37): ENSG00000185963
OMIM: 609797, Gene2Phenotype
BICD2 is in 9 panels

3 reviews

Rebecca Foulger (Genomics England curator)

Comment on list classification: Promoted BICD2 from Red to Green based on recent literature evidence and Green review by Zerin Hyder (Genomics England Clinical Team). Sufficient unrelated cases of AMC for inclusion on panel.
Created: 29 Nov 2019, 2:07 p.m. | Last Modified: 29 Nov 2019, 2:07 p.m.
Panel Version: 2.107

Zerin Hyder (Genomics England)

Green List (high evidence)

PMID:27751653 (Ravenscroft et al., 2016) report two unrelated probands (a German male and a boy from a Welsh mother and NZ/European father) that presented in utero with reduced fetal movement. Both cases had arthrogryposis multiplex congenita (AMC) and hypotonia diagnosed at birth . The same missense de novo variant in BICD2 (p.Arg694Cys) was present in both probands.
PMID:29274205 (Ahmed et al., 2018) report a stillborn female fetus (case 4) with pterygia and arthrogryposis with a heterozygous likely-pathogenic variant in BICD2. Phenotypes included an abnormal fetal position with fixed limbs, hydrops fetalis and polyhydramnios. A heterozygous p.Asn700Lys variant in BICD2 was revealed. However, compound het variants of unknown significance in AGRN were also identified, so the authors can not be certain that BICD2 is the causative variant.
PMID:28635954 (Storbeck et al., 2017) describe 3 individuals of independent families with severe arthrogryposis multiplex congenita (AMC), respiratory insufficiency, and early lethality caused by three BICD2 variants (p.Arg694Cys, p.Gln194Arg and p.Cys542Trp, 2 of which are proven to be de novo). They also describe an asymptomatic woman with subclinical findings with the previously described p.(Thr703Met) variant.
PMID: 30054298. In 2 unrelated patients with muscular atrophy and arthrogryposis Koboldt et al. (2018) identified a de novo heterozygous c.1636_1638delAAT variant in the BICD2 gene. The mutation, which was found by whole-exome or whole-genome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but protein modeling indicated that the variant is within a region that interacts with the molecular kinesin motor and that the mutation would alter protein structure.
Created: 29 Nov 2019, 2:02 p.m. | Last Modified: 29 Nov 2019, 2:03 p.m.
Panel Version: 2.104

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Spinal muscular atrophy, lower extremity-predominant, 2A, autosomal dominant 615290; Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291

Publications

Andrea Haworth (ACGS, Congenica)

Recent paper indicates a wide phenotypic spectrum for BICD2 from arthrogryposis to asymptomatic with variable expressivity within families.

European Journal of Human Genetics (2017) 25, 1040–1048
Phenotypic extremes of BICD2-opathies: from lethal,
congenital muscular atrophy with arthrogryposis to
asymptomatic with subclinical features
Markus Storbeck1,2,3, Beate Horsberg Eriksen4, Andreas Unger5, Irmgard Hölker1,2,3, Ingvild Aukrust6,
Lilian A Martínez-Carrera1,2,3, Wolfgang A Linke5, Andreas Ferbert7, Raoul Heller1, Matthias Vorgerd8,
Gunnar Houge6 and Brunhilde Wirth*,1,2,3
Created: 10 Aug 2017, 12:11 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert list
Phenotypes
  • arthrogryposis multiplex congenita
  • Spinal muscular atrophy, lower extremity-predominant, 2A, 615290
  • autosomal dominant, Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291
OMIM
609797
Clinvar variants
Variants in BICD2
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

29 Nov 2019, Gel status: 3

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: BICD2 were changed from Spinal muscular atrophy, lower extremity-predominant, 2A, 615290; autosomal dominant, Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291 to arthrogryposis multiplex congenita; Spinal muscular atrophy, lower extremity-predominant, 2A, 615290; autosomal dominant, Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291

29 Nov 2019, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: bicd2 has been classified as Green List (High Evidence).

29 Nov 2019, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: BICD2 were set to 28635954

29 Nov 2019, Gel status: 1

Set mode of inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for gene: BICD2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

29 Nov 2019, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: BICD2 were changed from Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291 to Spinal muscular atrophy, lower extremity-predominant, 2A, 615290; autosomal dominant, Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291

29 Nov 2019, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: BICD2 were changed from to Spinal muscular atrophy, lower extremity-predominant, 2B, autosomal dominant, 618291

29 Nov 2019, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: BICD2 were set to

16 Jan 2017, Gel status: 1

panel promoted to version 2

Ellen McDonagh (Genomics England Curator)

16th Jan 2016: This gene panel was extensively revised with the addition of 101 green genes and review by Alice Gardham. Due to this extensive change to the panel, the decision was made to promote it to the next major version, version 2.

21 Dec 2016, Gel status: 1

Gene classified by Genomics England curator

Alice Gardham (Genomics England)

This gene has been classified as Red List (Low Evidence).

21 Dec 2016, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

BICD2 was created by ellenmcdonagh

21 Dec 2016, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

BICD2 was added to Arthrogryposispanel. Sources: Expert list