ClinVar Miner

Submissions for variant NM_000123.4(ERCC5):c.2636A>G (p.Asn879Ser) (rs4150342)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000861048 SCV001001257 benign not provided 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001109872 SCV001267248 benign Xeroderma pigmentosum, group G 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
GeneDx RCV000861048 SCV001843699 benign not provided 2019-05-29 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 11841555, 24728327)
ITMI RCV000120835 SCV000085000 not provided not specified 2013-09-19 no assertion provided reference population
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000861048 SCV001550449 likely benign not provided no assertion criteria provided clinical testing The ERCC5 p.Asn879Ser variant was identified in dbSNP (ID: rs4150342) and ClinVar (submitted by ITMI with no classification) but was not identified in Cosmic or LOVD 3.0. The variant was identified in control databases in 2751 of 282866 chromosomes (15 homozygous) at a frequency of 0.009725 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 1776 of 129182 chromosomes (freq: 0.01375), Latino in 384 of 35438 chromosomes (freq: 0.01084), Other in 77 of 7224 chromosomes (freq: 0.01066), Ashkenazi Jewish in 95 of 10370 chromosomes (freq: 0.009161), European (Finnish) in 218 of 25122 chromosomes (freq: 0.008678), South Asian in 143 of 30616 chromosomes (freq: 0.004671), African in 56 of 24964 chromosomes (freq: 0.002243), and East Asian in 2 of 19950 chromosomes (freq: 0.0001). The variant was identified in a patient with Xeroderma Pigmentosum who also carried multiple other ERCC5 variants, therefore the N879S variant was not expected to have functional significance (Lalle_2002_PMID:11841555). The p.Asn879 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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