NM_000400.4:c.1119-102G>T
Variant names:
Variant summary
Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000400.4(ERCC2):c.1119-102G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 868,646 control chromosomes in the GnomAD database, including 147,608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.64 ( 32321 hom., cov: 31)
Exomes 𝑓: 0.56 ( 115287 hom. )
Consequence
ERCC2
NM_000400.4 intron
NM_000400.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.161
Publications
31 publications found
Genes affected
ERCC2 (HGNC:3434): (ERCC excision repair 2, TFIIH core complex helicase subunit) The nucleotide excision repair pathway is a mechanism to repair damage to DNA. The protein encoded by this gene is involved in transcription-coupled nucleotide excision repair and is an integral member of the basal transcription factor BTF2/TFIIH complex. The gene product has ATP-dependent DNA helicase activity and belongs to the RAD3/XPD subfamily of helicases. Defects in this gene can result in three different disorders, the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
ERCC2 Gene-Disease associations (from GenCC):
- cerebrooculofacioskeletal syndrome 2Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
- trichothiodystrophy 1, photosensitiveInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
- xeroderma pigmentosum group DInheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Laboratory for Molecular Medicine, ClinGen, Labcorp Genetics (formerly Invitae), G2P
- sarcomaInheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
- COFS syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- trichothiodystrophyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- xeroderma pigmentosumInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- xeroderma pigmentosum-Cockayne syndrome complexInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 19-45361744-C-A is Benign according to our data. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-45361744-C-A is described in CliVar as Benign. Clinvar id is 135529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.636 AC: 96572AN: 151800Hom.: 32270 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
96572
AN:
151800
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.581 AC: 117148AN: 201574 AF XY: 0.579 show subpopulations
GnomAD2 exomes
AF:
AC:
117148
AN:
201574
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.564 AC: 404426AN: 716726Hom.: 115287 Cov.: 9 AF XY: 0.566 AC XY: 215607AN XY: 380928 show subpopulations
GnomAD4 exome
AF:
AC:
404426
AN:
716726
Hom.:
Cov.:
9
AF XY:
AC XY:
215607
AN XY:
380928
show subpopulations
African (AFR)
AF:
AC:
16455
AN:
19108
American (AMR)
AF:
AC:
19499
AN:
37762
Ashkenazi Jewish (ASJ)
AF:
AC:
12435
AN:
20744
East Asian (EAS)
AF:
AC:
16823
AN:
34230
South Asian (SAS)
AF:
AC:
41386
AN:
68666
European-Finnish (FIN)
AF:
AC:
28093
AN:
47356
Middle Eastern (MID)
AF:
AC:
2515
AN:
4280
European-Non Finnish (NFE)
AF:
AC:
246954
AN:
449244
Other (OTH)
AF:
AC:
20266
AN:
35336
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
8774
17548
26322
35096
43870
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
3586
7172
10758
14344
17930
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome AF: 0.636 AC: 96676AN: 151920Hom.: 32321 Cov.: 31 AF XY: 0.634 AC XY: 47050AN XY: 74248 show subpopulations
GnomAD4 genome
AF:
AC:
96676
AN:
151920
Hom.:
Cov.:
31
AF XY:
AC XY:
47050
AN XY:
74248
show subpopulations
African (AFR)
AF:
AC:
35652
AN:
41426
American (AMR)
AF:
AC:
8050
AN:
15258
Ashkenazi Jewish (ASJ)
AF:
AC:
2039
AN:
3470
East Asian (EAS)
AF:
AC:
2566
AN:
5152
South Asian (SAS)
AF:
AC:
2836
AN:
4826
European-Finnish (FIN)
AF:
AC:
6259
AN:
10546
Middle Eastern (MID)
AF:
AC:
182
AN:
294
European-Non Finnish (NFE)
AF:
AC:
37322
AN:
67934
Other (OTH)
AF:
AC:
1253
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1631
3263
4894
6526
8157
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Genome Hom
Variant carriers
0
770
1540
2310
3080
3850
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1956
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Nov 11, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not specified Other:1
Sep 19, 2013
ITMI
Significance:not provided
Review Status:no classification provided
Collection Method:reference population
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
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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