Submissions for variant NM_014208.3(DSPP):c.2525del (p.Ser842fs)

gnomAD frequency: 0.00002  dbSNP: rs1395922945

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001008819	SCV001168620	likely pathogenic	not provided	2019-05-10	criteria provided, single submitter	clinical testing	The c.2525delG variant in the DSPP gene has been reported previously in four families with dentiogenesis imperfecta who all had the same haplotype, suggesting c.2525delG is a founder mutation in Northern European Caucasians (McKnight et al., 2008). The c.2525delG variant causes a frameshift starting with codon Serine 842, changes this amino acid to a Threonine residue, and creates a premature Stop codon at position 472 of the new reading frame, denoted p.Ser842ThrfsX472. This variant is predicted to cause loss of normal protein function through protein truncation, as the last 460 amino acids are lot and replaced with 471 incorrect amino acids. Although not observed as homozygous, the c.2525delG variant is observed in 1/14934 (0.0067%) alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016). We interpret c.2525delG as a likely pathogenic variant.
Fulgent Genetics, Fulgent Genetics	RCV002497332	SCV002810376	pathogenic	Deafness, autosomal dominant 39, with dentinogenesis imperfecta 1; Dentinogenesis imperfecta type 2; Denticles; Dentinogenesis imperfecta type 3	2021-11-10	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV004545813	SCV001423430	not provided	DSPP-related disorder		no assertion provided	phenotyping only	Variant interpretted as Likely pathogenic and reported on 05-21-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.