Genes in panel

Hereditary ataxia - adult onset

Gene: XRCC1

Amber List (moderate evidence)

XRCC1 (X-ray repair cross complementing 1)
EnsemblGeneIds (GRCh38): ENSG00000073050
EnsemblGeneIds (GRCh37): ENSG00000073050
OMIM: 194360, Gene2Phenotype
XRCC1 is in 6 panels

5 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 9 Mar 2022, 5:26 p.m. | Last Modified: 9 Mar 2022, 5:26 p.m.
Panel Version: 2.144

Arina Puzriakova (Genomics England Curator)

Comment on list classification: This gene will be flagged for GMS review to determine whether there is enough evidence to include XRCC1 on this panel as Green. Only one case with adult onset and the other two with onset in childhood, however inclusion may be justified to ensure identification of edge cases.
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Three individuals from unrelated families all from South Asian descent with cerebellar ataxia and peripheral neuropathy and a recurrent variant (c.1293G>C, 2 homozygotes and a comp het) in the XRCC1 gene. Homozygosity mapping in 2 families confirmed a shared haplotype and the recurrent variant is found in a heterozygous state in an unaffected sib and 4 individuals of South Asian descent in ExAC - indicating that this is a founder variant that is pathogenic when when in trans with a second variant. There is some strong functional evidence that supports pathogenicity, including an animal model that recapitulated human phenotypes such as cerebellar ataxia.
Created: 28 Jun 2021, 3:42 p.m. | Last Modified: 28 Jun 2021, 3:42 p.m.
Panel Version: 2.80

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spinocerebellar ataxia, autosomal recessive 26, OMIM:617633

Publications

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Red List (low evidence)

Single East Indian family. Not on Ox or Shef. Mismatch repair gene.
Created: 27 Apr 2019, 7:39 p.m.

Louise Daugherty (Genomics England Curator)

I don't know

Added watchlist tag. As discussed with the GMS Neurology Specialist Test Group webex call 26th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Amber
Created: 1 Aug 2019, 3:43 p.m. | Last Modified: 1 Aug 2019, 3:43 p.m.
Panel Version: 1.188
Review and rating submitted by James Polke (Neurogenetics Laboratory, Institute of Neurology, London) on behalf of London North GLH for GMS Neurology specialist test group
Created: 27 Apr 2019, 8:55 p.m.
Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.
Created: 15 Apr 2019, 10:21 a.m.

Tracy Lester (Genetics laboratory, Oxford UK)

I don't know

Only a single individual reported, compound het for LoF variants. VERY strong functional evidence.
Created: 15 Apr 2019, 10:06 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Autosomal recessive spinocerebellar ataxia 26, 617633

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • London North GLH
  • NHS GMS
  • Wessex and West Midlands GLH
  • Hereditary ataxia v1.148
Phenotypes
  • Spinocerebellar ataxia, autosomal recessive 26, OMIM:617633
Tags
founder-effect
OMIM
194360
Clinvar variants
Variants in XRCC1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

9 Mar 2022, Gel status: 2

Removed Tag

Eleanor Williams (Genomics England Curator)

Tag Q2_21_expert_review was removed from gene: XRCC1.

28 Jun 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_expert_review tag was added to gene: XRCC1.

28 Jun 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: xrcc1 has been classified as Amber List (Moderate Evidence).

28 Jun 2021, Gel status: 2

Removed Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist was removed from gene: XRCC1. Tag founder-effect tag was added to gene: XRCC1.

28 Jun 2021, Gel status: 2

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: XRCC1 were set to 28002403

28 Jun 2021, Gel status: 2

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: XRCC1 were changed from ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia; Autosomal recessive spinocerebellar ataxia 26, 617633 to Spinocerebellar ataxia, autosomal recessive 26, OMIM:617633

1 Aug 2019, Gel status: 2

Added Tag

Louise Daugherty (Genomics England Curator)

Tag watchlist tag was added to gene: XRCC1.

27 Apr 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: xrcc1 has been classified as Amber List (Moderate Evidence).

27 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GMS was added to XRCC1.

15 Apr 2019, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Added phenotypes Autosomal recessive spinocerebellar ataxia 26, 617633 for gene: XRCC1

14 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to XRCC1.

14 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source Wessex and West Midlands GLH was added to XRCC1.

9 Jan 2019, Gel status: 1

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

Louise Daugherty: Comment on phenotypes: Implica

15 Dec 2018, Gel status: 1

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

Eleanor Williams (Genomics England Curator)

gene: XRCC1 was added gene: XRCC1 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red Mode of inheritance for gene: XRCC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: XRCC1 were set to 28002403 Phenotypes for gene: XRCC1 were set to ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia