Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000877004 | SCV001019663 | likely benign | not provided | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV000877004 | SCV001550605 | uncertain significance | not provided | no assertion criteria provided | clinical testing | The CHRNG p.Gln238His variant was not identified in the literature nor was it identified in LOVD 3.0. The variant was identified in dbSNP (ID: rs17838626) and ClinVar (classified as likely benign by Invitae). The variant was identified in control databases in 233 of 282892 chromosomes at a frequency of 0.0008236 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: African in 202 of 24968 chromosomes (freq: 0.00809), Latino in 21 of 35438 chromosomes (freq: 0.000593), Other in 3 of 7228 chromosomes (freq: 0.000415) and European (non-Finnish) in 7 of 129198 chromosomes (freq: 0.000054), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), or South Asian populations. The p.Gln238 residue is 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 2 of 4 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. This variant is classified as a variant of uncertain significance. |