Submissions for variant NM_001378615.1(CC2D2A):c.1730C>T (p.Ser577Leu)

gnomAD frequency: 0.00002  dbSNP: rs543650388

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001145126	SCV001305768	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.
Illumina Laboratory Services, Illumina	RCV001145127	SCV001305769	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.
Invitae	RCV002032368	SCV002290836	likely benign	Familial aplasia of the vermis; Meckel-Gruber syndrome	2024-01-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002557107	SCV003730702	uncertain significance	Inborn genetic diseases	2021-10-12	criteria provided, single submitter	clinical testing	The c.1730C>T (p.S577L) alteration is located in exon 16 (coding exon 14) of the CC2D2A gene. This alteration results from a C to T substitution at nucleotide position 1730, causing the serine (S) at amino acid position 577 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003413953	SCV004106804	uncertain significance	CC2D2A-related condition	2022-11-17	criteria provided, single submitter	clinical testing	The CC2D2A c.1730C>T variant is predicted to result in the amino acid substitution p.Ser577Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.026% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-15538665-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.