Submissions for variant NM_001171.6(ABCC6):c.2695C>T (p.Arg899Cys)

gnomAD frequency: 0.00098  dbSNP: rs11861980

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000881901	SCV001025101	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002487931	SCV002799001	likely benign	Autosomal recessive inherited pseudoxanthoma elasticum; Pseudoxanthoma elasticum, forme fruste; Arterial calcification, generalized, of infancy, 2	2022-05-18	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000881901	SCV005213410	likely benign	not provided		criteria provided, single submitter	not provided
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000881901	SCV001551937	uncertain significance	not provided		no assertion criteria provided	clinical testing	The ABCC6 p.Arg785Cys variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs11861980) and LOVD 3.0 (not classified). The variant was identified in control databases in 99 of 282760 chromosomes at a frequency of 0.0003501 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 96 of 24936 chromosomes (freq: 0.00385) and Latino in 3 of 35426 chromosomes (freq: 0.000085), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), European (non-Finnish), Other, and South Asian populations. The p.Arg785 residue is not 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.
PreventionGenetics, part of Exact Sciences	RCV004530908	SCV004741060	likely benign	ABCC6-related disorder	2022-06-01	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).