Submissions for variant NM_001122630.2(CDKN1C):c.573GGCCCC[2] (p.186AP[8])

dbSNP: rs759134767

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000232076	SCV000283420	benign	Beckwith-Wiedemann syndrome	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000246892	SCV000301916	benign	not specified		criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000246892	SCV000333244	benign	not specified	2015-07-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001358515	SCV001825822	likely benign	not provided	2021-03-16	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000246892	SCV002070467	benign	not specified	2017-11-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001358515	SCV002497100	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	CDKN1C: BS1, BS2
Sema4, Sema4	RCV000232076	SCV002534288	benign	Beckwith-Wiedemann syndrome	2020-02-24	criteria provided, single submitter	curation
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001358515	SCV001554271	likely benign	not provided		no assertion criteria provided	clinical testing	The CDKN1C p.Ala213_Pro216del variant was not identified in the literature nor was it identified in Cosmic. The variant was identified in dbSNP (ID: rs759134767), ClinVar (classified as benign by Invitae, Prevention Genetics and EGL Genetic Diagnostics) and LOVD 3.0. The variant was identified in control databases in 415 of 25528 chromosomes (6 homozygous) at a frequency of 0.016257 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 344 of 13620 chromosomes (freq: 0.02526), Ashkenazi Jewish in 6 of 258 chromosomes (freq: 0.02326), Latino in 6 of 416 chromosomes (freq: 0.01442), Other in 10 of 752 chromosomes (freq: 0.0133), European (Finnish) in 6 of 962 chromosomes (freq: 0.006237) and African in 43 of 7844 chromosomes (freq: 0.005482); it was not observed in the East Asian or South Asian populations. The variant occurs outside the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. This variant is an in-frame deletion resulting in the removal of the APAP residues between codons 213-216 in a non-conserved repeat region with unknown function. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. Therefore it is classified as likely benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001358515	SCV001798063	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000246892	SCV001931233	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000246892	SCV001968360	benign	not specified		no assertion criteria provided	clinical testing