NM_000082.4:c.600dupT
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000082.4(ERCC8):c.600dupT(p.Ile201TyrfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,090 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Consequence
ERCC8
NM_000082.4 frameshift
NM_000082.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.31
Publications
2 publications found
Genes affected
ERCC8 (HGNC:3439): (ERCC excision repair 8, CSA ubiquitin ligase complex subunit) This gene encodes a WD repeat protein, which interacts with Cockayne syndrome type B (CSB) protein and with p44 protein, a subunit of the RNA polymerase II transcription factor IIH. Mutations in this gene have been identified in patients with hereditary disease Cockayne syndrome (CS). CS cells are abnormally sensitive to ultraviolet radiation and are defective in the repair of transcriptionally active genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2014]
ERCC8 Gene-Disease associations (from GenCC):
- Cockayne syndrome type 1Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Laboratory for Molecular Medicine, Myriad Women’s Health, ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
- UV-sensitive syndrome 2Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
- Cockayne syndrome type 2Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- UV-sensitive syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 5-60902458-T-TA is Pathogenic according to our data. Variant chr5-60902458-T-TA is described in ClinVar as Pathogenic. ClinVar VariationId is 553300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000082.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ERCC8 | NM_000082.4 | MANE Select | c.600dupT | p.Ile201TyrfsTer8 | frameshift | Exon 7 of 12 | NP_000073.1 | Q13216-1 | |
| ERCC8 | NM_001007233.3 | c.426dupT | p.Ile143TyrfsTer8 | frameshift | Exon 8 of 13 | NP_001007234.1 | B3KPW7 | ||
| ERCC8 | NM_001290285.2 | c.141dupT | p.Ile48TyrfsTer8 | frameshift | Exon 6 of 11 | NP_001277214.1 | B4DGZ9 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ERCC8 | ENST00000676185.1 | MANE Select | c.600dupT | p.Ile201TyrfsTer8 | frameshift | Exon 7 of 12 | ENSP00000501614.1 | Q13216-1 | |
| ERCC8 | ENST00000265038.10 | TSL:1 | c.600dupT | p.Ile201TyrfsTer8 | frameshift | Exon 7 of 13 | ENSP00000265038.6 | A0A7I2PE23 | |
| ERCC8 | ENST00000891473.1 | c.612dupT | p.Ile205TyrfsTer8 | frameshift | Exon 7 of 12 | ENSP00000561532.1 |
Frequencies
GnomAD3 genomes 0.0000197 AC: 3AN: 152090Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
152090
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
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Gnomad SAS
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
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GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome 0.0000197 AC: 3AN: 152090Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74294 show subpopulations
GnomAD4 genome
AF:
AC:
3
AN:
152090
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74294
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41444
American (AMR)
AF:
AC:
2
AN:
15272
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3468
East Asian (EAS)
AF:
AC:
0
AN:
5206
South Asian (SAS)
AF:
AC:
0
AN:
4838
European-Finnish (FIN)
AF:
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67924
Other (OTH)
AF:
AC:
0
AN:
2086
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
2
-
-
Cockayne syndrome type 1 (2)
2
-
-
not provided (2)
1
-
-
Cockayne syndrome type 1;C3553298:UV-sensitive syndrome 2 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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