ClinVar Miner

Submissions for variant NM_002273.4(KRT8):c.184G>T (p.Gly62Cys)

gnomAD frequency: 0.00545  dbSNP: rs11554495
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV002247346 SCV002518578 benign not specified 2022-05-04 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000056938 SCV004133387 likely benign not provided 2023-07-01 criteria provided, single submitter clinical testing KRT8: BS2
Invitae RCV000056938 SCV004467466 benign not provided 2023-12-23 criteria provided, single submitter clinical testing
OMIM RCV000015735 SCV000036000 uncertain significance Cirrhosis, cryptogenic 2003-05-13 no assertion criteria provided literature only
Epithelial Biology; Institute of Medical Biology, Singapore RCV000056938 SCV000088051 not provided not provided no assertion provided not provided
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000056938 SCV001553834 likely benign not provided no assertion criteria provided clinical testing The KRT8 p.Gly62Cys variant was identified in 33 of 4270 proband chromosomes (frequency: 0.0077) from individuals with liver disease but was also present in 13 of 2056 control chromosomes (frequency: 0.0063) from healthy individuals, suggesting no association with liver disease (Halangk_2004_PMID:15235035; Ku_2003_PMID:12724528). Analysis of the p.G62C variant in a cohort of 217 German patients with Crohn' s disease, 131 German patients with ulcerative colitis, and 560 German control subjects also did not identify an association of this variant with Crohn's or ulcerative colitis (Büning_2004_PMID:15248378). The variant was identified in dbSNP (ID: rs11554495), ClinVar (classification not provided by Epithelial Biology; Institute of Medical Biology, Singapore) and LOVD 3.0 (classified as likely benign). The variant was identified in control databases in 1370 of 280620 chromosomes (7 homozygous) at a frequency of 0.004882 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 1176 of 127714 chromosomes (freq: 0.009208), Other in 37 of 7182 chromosomes (freq: 0.005152), African in 44 of 24386 chromosomes (freq: 0.001804), Latino in 60 of 35410 chromosomes (freq: 0.001694), European (Finnish) in 33 of 25106 chromosomes (freq: 0.001314), Ashkenazi Jewish in 5 of 10294 chromosomes (freq: 0.000486), South Asian in 14 of 30600 chromosomes (freq: 0.000458), and East Asian in 1 of 19928 chromosomes (freq: 0.00005). Although the p.Gly62 residue is not conserved in mammals and other organisms, computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein. The variant occurs outside of the splicing consensus sequence and two of four in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.