ClinVar Miner

Submissions for variant NM_000158.4(GBE1):c.2035C>T (p.Arg679Cys) (rs202158511)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000297840 SCV000446281 likely benign Glycogen storage disease, type IV 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000357256 SCV000446282 likely benign Adult polyglucosan body disease 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae RCV000966281 SCV001113579 benign Glycogen storage disease, type IV; Glycogen storage disease IV, classic hepatic 2020-11-17 criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV000297840 SCV001653468 uncertain significance Glycogen storage disease, type IV 2021-05-18 criteria provided, single submitter clinical testing
Natera, Inc. RCV000297840 SCV001460899 benign Glycogen storage disease, type IV 2020-06-04 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354590 SCV001549239 likely benign not provided no assertion criteria provided clinical testing The GBE1 p.Arg679Cys variant was not identified in the literature but was identified in dbSNP (ID: rs202158511) and ClinVar (classified as uncertain significance by Illumina and as benign by Invitae). The variant was identified in control databases in 145 of 273980 chromosomes (2 homozygous) at a frequency of 0.0005292 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: South Asian in 121 of 29454 chromosomes (freq: 0.004108), East Asian in 4 of 19138 chromosomes (freq: 0.000209), Latino in 7 of 34592 chromosomes (freq: 0.000202), Other in 1 of 6970 chromosomes (freq: 0.000144) and European (non-Finnish) in 12 of 125122 chromosomes (freq: 0.000096), but was not observed in the African, Ashkenazi Jewish, or European (Finnish) populations. The p.Arg679 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of 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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