Submissions for variant NM_001378615.1(CC2D2A):c.3670C>T (p.Arg1224Trp)

gnomAD frequency: 0.00002  dbSNP: rs369648324

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000268647	SCV000448058	uncertain significance	Joubert syndrome 9	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000323676	SCV000448059	uncertain significance	CC2D2A-related disorder	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000373501	SCV000448060	uncertain significance	Meckel syndrome, type 6	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002520220	SCV003479504	likely benign	Familial aplasia of the vermis; Meckel-Gruber syndrome	2024-10-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002520221	SCV003552645	uncertain significance	Inborn genetic diseases	2021-06-18	criteria provided, single submitter	clinical testing	The c.3670C>T (p.R1224W) alteration is located in exon 30 (coding exon 28) of the CC2D2A gene. This alteration results from a C to T substitution at nucleotide position 3670, causing the arginine (R) at amino acid position 1224 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV000323676	SCV004710983	uncertain significance	CC2D2A-related disorder	2023-12-12	no assertion criteria provided	clinical testing	The CC2D2A c.3670C>T variant is predicted to result in the amino acid substitution p.Arg1224Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.037% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-15575848-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.