Submissions for variant NM_015570.4(AUTS2):c.1603_1626del (p.531HQHT[1])

dbSNP: rs1789934246

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001266310	SCV001444483	uncertain significance	Inborn genetic diseases	2020-08-04	criteria provided, single submitter	clinical testing	The alteration results in an in-frame deletion:_x000D_ _x000D_ The c.1603_1626del24 (p.H535_T542del) alteration is located in coding exon 9 of the AUTS2 gene. This alteration results from an in-frame deletion of 24 nucleotides at positions c.1603 to c.1626, resulting in the deletion of 8 amino acids at codons 535 to 542. The alteration is not observed in population databases:_x000D_ _x000D_ Based on data from the Genome Aggregation Database (gnomAD), the AUTS2 c.1603_1626del24 alteration was not observed, with coverage at this position The alteration is predicted deleterious by in silico models:_x000D_ _x000D_ The p.H535_T542del alteration is predicted to be deleterious with a score of -42.658 by PROVEAN in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001302562	SCV001491776	uncertain significance	not provided	2024-08-19	criteria provided, single submitter	clinical testing	This variant, c.1603_1626del, results in the deletion of 8 amino acid(s) of the AUTS2 protein (p.His535_Thr542del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with AUTS2 syndrome and/or clinical features of AUTS2-related conditions (PMID: 33562463, 35032046). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 984610). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Genetics Laboratory, UDIAT-Centre Diagnòstic, Hospital Universitari Parc Tauli	RCV001420233	SCV001622653	pathogenic	See cases	2021-04-26	criteria provided, single submitter	clinical testing	PS3_strong;PM1_moderate;PM2_supporting;PM4_moderate;PM6_moderate;PP3_supporting
GeneDx	RCV001302562	SCV001770714	pathogenic	not provided	2023-05-23	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 35032046, 33562463)
Revvity Omics, Revvity	RCV003145502	SCV003834547	uncertain significance	Autism spectrum disorder due to AUTS2 deficiency	2020-03-16	criteria provided, single submitter	clinical testing
Duke University Health System Sequencing Clinic, Duke University Health System	RCV003145502	SCV003918963	pathogenic	Autism spectrum disorder due to AUTS2 deficiency	2023-04-20	criteria provided, single submitter	research
Baylor Genetics	RCV003145502	SCV004183488	pathogenic	Autism spectrum disorder due to AUTS2 deficiency	2023-09-05	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV003145502	SCV005416043	likely pathogenic	Autism spectrum disorder due to AUTS2 deficiency		criteria provided, single submitter	clinical testing	PM2_Supporting+PM4+PS2_Supporting+PS4_Supporting+PP4
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine	RCV001264706	SCV001442889	likely pathogenic	Neurodevelopmental abnormality	2020-04-03	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004746301	SCV005362519	likely pathogenic	AUTS2-related disorder	2024-05-02	no assertion criteria provided	clinical testing	The AUTS2 c.1603_1626del24 variant is predicted to result in an in-frame deletion (p.His535_Thr542del). This variant was reported in two individuals with a neurodevelopmental disorder phenotype (Table S1, Sukenik-Halevy et al. 2022. PubMed ID: 35032046; de novo, Palumbo et al. 2021. PubMed ID: 33562463). At PreventionGenetics, we have also observed this variant to occur de novo in an individual with a neurodevelopmental disorder phenotype (internal data). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as likely pathogenic.