Submissions for variant NM_015102.5(NPHP4):c.871_889delinsC (p.Val291_Phe297delinsLeu)

dbSNP: rs1553186265

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000638085	SCV000759565	uncertain significance	Nephronophthisis	2018-01-23	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the disrupted amino acids is currently unknown. This variant has not been reported in the literature in individuals with NPHP4-related disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant, c.871_889delinsC, is a complex sequence change that results in the deletion of 7 amino acids and the insertion of 1 amino acid to the NPHP4 protein (p.Val291_Phe297delinsLeu), but otherwise preserves the integrity of the reading frame.
Sydney Genome Diagnostics, Children's Hospital Westmead	RCV000638085	SCV001449372	uncertain significance	Nephronophthisis	2018-02-21	no assertion criteria provided	clinical testing	This individual is heterozygous for the c.871_889delinsC variant in the NPHP4 gene. This in-frame variant results in the replacement of 7 amino acids Val291 to Phe297 with a single leucine residue. This variant has not been reported in any population databases (i.e. ExAC, ESP or dbSNP). To our knowledge, this variant has not been previously reported in the literature or any disease specific databases. This variant is considered to be a variant of uncertain significance (VOUS) according to the ACMG guidelines.