Submissions for variant NM_001378615.1(CC2D2A):c.2056G>A (p.Val686Met)

gnomAD frequency: 0.00027  dbSNP: rs369476930

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000298157	SCV000447755	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	RCV000336743	SCV000447756	uncertain significance	CC2D2A-related disorder	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000394824	SCV000447757	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.
Eurofins Ntd Llc (ga)	RCV000731265	SCV000859061	uncertain significance	not provided	2018-01-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001038299	SCV001201764	likely benign	Familial aplasia of the vermis; Meckel-Gruber syndrome	2024-12-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000731265	SCV002571679	uncertain significance	not provided	2022-09-06	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002520210	SCV003692183	uncertain significance	Inborn genetic diseases	2022-08-18	criteria provided, single submitter	clinical testing	The c.2056G>A (p.V686M) alteration is located in exon 18 (coding exon 16) of the CC2D2A gene. This alteration results from a G to A substitution at nucleotide position 2056, causing the valine (V) at amino acid position 686 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Clinical Genetics, Academic Medical Center	RCV000731265	SCV001926061	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000731265	SCV001968014	uncertain significance	not provided		no assertion criteria provided	clinical testing