This variant, c.4626_4631del, results in the deletion of 2 amino acid(s) of the ATRX protein (p.Asp1542_Glu1543del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with moderate mental retardation, expressive language delay, HbH inclusions, and hypospodia (PMID: 11449489). This variant is also known as c.4832_4837del; p.1540_1541delDE. ClinVar contains an entry for this variant (Variation ID: 210497). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects ATRX function (PMID: 21505078). 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.
ClinVar Genomic variation as it relates to human health
Help
- Interpretation:
-
Conflicting interpretations of pathogenicity
Pathogenic(1); Likely pathogenic(1); Uncertain significance(1)
- Review status:
- criteria provided, conflicting interpretations
- Submissions:
- 3
- First in ClinVar:
- Nov 10, 2017
- Most recent Submission:
- Nov 25, 2023
- Last evaluated:
- May 9, 2023
- Accession:
- VCV000210497.14
- Variation ID:
- 210497
- Description:
- 6bp microsatellite
Help
NM_000489.6(ATRX):c.4620TGAAGA[1] (p.1540DE[1])
- Allele ID
- 209199
- Variant type
- Microsatellite
- Variant length
- 6 bp
- Cytogenetic location
- Xq21.1
- Genomic location
- X: 77635983-77635988 (GRCh38) GRCh38 UCSC
- X: 76891474-76891479 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000489.6:c.4620TGAAGA[1] MANE Select NP_000480.3:p.1540DE[1] inframe deletion NM_138270.5:c.4506TGAAGA[1] NP_612114.2:p.1502DE[1] inframe deletion NC_000023.11:g.77635986TCATCT[1] NC_000023.10:g.76891477TCATCT[1] NG_008838.3:g.155276TGAAGA[1] LRG_1153:g.155276TGAAGA[1] - Protein change
- -
- Other names
- -
- Canonical SPDI
- NC_000023.11:77635982:TCTTCATCTTCATCT:TCTTCATCT
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- ClinGen: CA277098
- dbSNP: rs797045406
- VarSome
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Uncertain significance | 1 | criteria provided, single submitter | Aug 12, 2021 | RCV000798266.13 | |
| Pathogenic | 1 | criteria provided, single submitter | Dec 21, 2016 | RCV002051688.11 | |
| Likely pathogenic | 1 | criteria provided, single submitter | May 9, 2023 | RCV003441774.1 |
Help
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation viewer | Related variants | ||
|---|---|---|---|---|---|---|
| HI score Help | TS score Help | Within gene | All | |||
| ATRX | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
1766 | 1926 | |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Pathogenic
(Dec 21, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: yes
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000246760.2
First in ClinVar: Oct 05, 2015 Last updated: Nov 10, 2017 |
|
|
|
Uncertain significance
(Aug 12, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000937872.3
First in ClinVar: Aug 14, 2019 Last updated: Feb 07, 2023 |
Comment:
This variant, c.4626_4631del, results in the deletion of 2 amino acid(s) of the ATRX protein (p.Asp1542_Glu1543del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.4626_4631del, results in the deletion of 2 amino acid(s) of the ATRX protein (p.Asp1542_Glu1543del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with moderate mental retardation, expressive language delay, HbH inclusions, and hypospodia (PMID: 11449489). This variant is also known as c.4832_4837del; p.1540_1541delDE. ClinVar contains an entry for this variant (Variation ID: 210497). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects ATRX function (PMID: 21505078). 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. (less)
|
|
|
Likely pathogenic
(May 09, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV004169631.1
First in ClinVar: Nov 25, 2023 Last updated: Nov 25, 2023 |
Comment:
In-frame deletion of 2 amino acids in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with … (more)
In-frame deletion of 2 amino acids in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 21505078, 33176815, 11449489) (less)
|
Functional evidence
Help| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Functional significance of mutations in the Snf2 domain of ATRX. | Mitson M | Human molecular genetics | 2011 | PMID: 21505078 |
| Molecular-clinical spectrum of the ATR-X syndrome. | Gibbons RJ | American journal of medical genetics | 2000 | PMID: 11449489 |
Text-mined citations for rs797045406...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Dec 02, 2023