Submissions for variant NM_001282531.3(ADNP):c.819del (p.Lys274fs)

dbSNP: rs886041498

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000362536	SCV000330163	pathogenic	not provided	2017-01-04	criteria provided, single submitter	clinical testing	The c.819delC variant in the ADNP gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.819delC variant causes a frameshift starting with codon Lysine 274, changes this amino acid to an Asparagine residue, and creates a premature Stop codon at position 31 of the new reading frame, denoted p.Lys274AsnfsX31. This variant is predicted to cause loss of normal protein function through protein truncation. The c.819delC variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Protein truncating pathogenic variants downstream of this variant have been reported in the Human Gene Mutation Database in association with ADNP-related disorders (Stenson et al., 2014), supporting the pathogenicity of more upstream truncating variants. We interpret c.819delC as a pathogenic variant.
GenomeConnect - Simons Searchlight	RCV001265360	SCV001443480	pathogenic	ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder	2016-02-16	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2016-02-16 and interpreted as Pathogenic. Variant was initially reported on 2016-01-16 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar.