ClinVar Miner

Submissions for variant NM_001286577.2(C2CD3):c.8A>C (p.Gln3Pro)

gnomAD frequency: 0.00004  dbSNP: rs370689810
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001358414 SCV002275864 uncertain significance not provided 2022-07-05 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1050686). This variant has not been reported in the literature in individuals affected with C2CD3-related conditions. This variant is present in population databases (rs370689810, gnomAD 0.02%). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 3 of the C2CD3 protein (p.Gln3Pro).
Ambry Genetics RCV004968116 SCV005549738 uncertain significance Inborn genetic diseases 2024-09-06 criteria provided, single submitter clinical testing The c.8A>C (p.Q3P) alteration is located in exon 1 (coding exon 1) of the C2CD3 gene. This alteration results from a A to C substitution at nucleotide position 8, causing the glutamine (Q) at amino acid position 3 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001358414 SCV001554139 uncertain significance not provided no assertion criteria provided clinical testing The C2CD3 p.Gln3Pro variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs370689810) and in control databases in 5 of 282808 chromosomes at a frequency of 0.00001768 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 4 of 24956 chromosomes (freq: 0.00016) and Latino in 1 of 35440 chromosomes (freq: 0.000028), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Other, or South Asian populations. The p.Gln3Pro 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 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. This variant is classified as a variant of uncertain significance.

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