Submissions for variant NM_001282531.3(ADNP):c.517C>T (p.Arg173Ter)

dbSNP: rs1135401791

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement, Assistance Publique Hopitaux de Paris	RCV000496157	SCV000586746	pathogenic	ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder	2017-01-06	criteria provided, single submitter	clinical testing	Intellectual disability
GeneDx	RCV001008669	SCV001168448	pathogenic	not provided	2019-03-04	criteria provided, single submitter	clinical testing	The R173X nonsense variant in the ADNP gene has been previously reported in association with HVDAS (Cherot et al., 2018). This pathogenic variant is predicted to cause loss of normal protein function through protein truncation as the last 930 amino acid residues of the ADNP protein are lost. The R173X variant is not observed in large population cohorts (Lek et al., 2016). Additionally, the R173X variant has occurred de novo in this individual whose reported clinical presentation is consistent with Helsmoortel-van der Aa syndrome. Therefore, R173X is considered a pathogenic variant.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV000496157	SCV001870317	pathogenic	ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder	2020-03-27	criteria provided, single submitter	research	ACMG codes:PVS1, PS2, PS4, PM2