Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001983.4(ERCC1):c.184G>T(p.Glu62*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
ERCC1 (HGNC:3433): (ERCC excision repair 1, endonuclease non-catalytic subunit) The product of this gene functions in the nucleotide excision repair pathway, and is required for the repair of DNA lesions such as those induced by UV light or formed by electrophilic compounds including cisplatin. The encoded protein forms a heterodimer with the XPF endonuclease (also known as ERCC4), and the heterodimeric endonuclease catalyzes the 5' incision in the process of excising the DNA lesion. The heterodimeric endonuclease is also involved in recombinational DNA repair and in the repair of inter-strand crosslinks. Mutations in this gene result in cerebrooculofacioskeletal syndrome, and polymorphisms that alter expression of this gene may play a role in carcinogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. The last exon of this gene overlaps with the CD3e molecule, epsilon associated protein gene on the opposite strand. [provided by RefSeq, Oct 2009]
ERCC1 Gene-Disease associations (from GenCC):
cerebrooculofacioskeletal syndrome 4
Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
Cockayne syndrome type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
COFS syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Our verdict: Pathogenic. The variant received 12 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 19-45421315-C-A is Pathogenic according to our data. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-45421315-C-A is described in CliVar as Likely_pathogenic. Clinvar id is 225348.Status of the report is criteria_provided_single_submitter, 1 stars.