Genes in panel

Ataxia and cerebellar anomalies - narrow panel

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

2 reviews

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Following discussion with Helen Brittain (Genomics England Clinical Team) it was agreed that there is enough evidence to promote this gene to Green at the next GMS panel update (see details below).
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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, 3:32 p.m. | Last Modified: 28 Jun 2021, 3:36 p.m.
Panel Version: 2.214

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spinocerebellar ataxia, autosomal recessive 26, OMIM:617633

Publications

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Three South Asian cases (one with early adult onset and the other two with onset in childhood) reported with slowly progressive cerebellar ataxia accompanied by sensorimotor neuropathy. All with the recurrent splice variant (c.1293G>C, 2 homozygotes and a compound heterozygote). Mice with conditional deletion of the Xrcc1 gene in the brain showed cerebellar ataxia.
Created: 13 Sep 2020, 8:02 a.m. | Last Modified: 13 Sep 2020, 8:02 a.m.
Panel Version: 2.12

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spinocerebellar ataxia, autosomal recessive 26 MIM#617633

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Spinocerebellar ataxia, autosomal recessive 26, OMIM:617633
Tags
founder-effect Q2_21_rating
OMIM
194360
Clinvar variants
Variants in XRCC1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

28 Jun 2021, Gel status: 2

Added Tag, Added Tag

Arina Puzriakova (Genomics England Curator)

Tag founder-effect tag was added to gene: XRCC1. Tag Q2_21_rating 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: 1

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: XRCC1 were set to 28002403

28 Jun 2021, Gel status: 1

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

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

9 Jan 2019, Gel status: 1

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

Rebecca Foulger: Comment on list classification

19 Dec 2018, Gel status: 1

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

Ellen McDonagh (Genomics England Curator)

gene: XRCC1 was added gene: XRCC1 was added to Ataxia and cerebellar anomalies - narrow panel. Sources: 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