ClinVar Miner

Submissions for variant NM_000489.6(ATRX):c.7156C>T (p.Arg2386Ter)

dbSNP: rs122445099
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000723525 SCV000331241 pathogenic not provided 2016-04-25 criteria provided, single submitter clinical testing
Center for Personalized Medicine, Children's Hospital Los Angeles RCV000735339 SCV000854495 pathogenic Cryptorchidism; Bone osteosarcoma; Ambiguous genitalia; Microcephaly; Intellectual disability, severe criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000723525 SCV001448164 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Invitae RCV000012494 SCV002230912 pathogenic Alpha thalassemia-X-linked intellectual disability syndrome 2024-01-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2386*) in the ATRX gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 107 amino acid(s) of the ATRX protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with alpha-thalassemia X-linked intellectual disability syndrome (PMID: 7697714, 24690944, 28371217). It has also been observed to segregate with disease in related individuals. This variant is also known as C4635T (R1528*). ClinVar contains an entry for this variant (Variation ID: 11728). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
3billion RCV002283442 SCV002572629 pathogenic Intellectual disability-hypotonic facies syndrome, X-linked, 1 2022-09-01 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Stop-gained (nonsense) is predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by less than 10%. The variant has been observed in at least two similarly affected unrelated individuals (PMID: 24690944 , 28371217 , 7697714). The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000011728 / PMID: 7697714). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Center for Personalized Medicine, Children's Hospital Los Angeles RCV003156057 SCV003845256 pathogenic See cases 2022-12-21 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004532323 SCV004120580 pathogenic ATRX-related disorder 2024-03-01 criteria provided, single submitter clinical testing The ATRX c.7156C>T variant is predicted to result in premature protein termination (p.Arg2386*). This variant has been reported in multiple individuals with X-linked intellectual disability syndrome (Gibbons et al 1995. PubMed ID: 7697714; Brett M et al 2014. PubMed ID: 24690944; Ji J et al 2017. PubMed ID: 28371217). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in ATRX are expected to be pathogenic. This variant is interpreted as pathogenic.
OMIM RCV000012494 SCV000032728 pathogenic Alpha thalassemia-X-linked intellectual disability syndrome 1995-03-24 no assertion criteria provided literature only

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