NM_000489.6(ATRX):c.7156C>T (p.Arg2386Ter) AND Intellectual disability-hypotonic facies syndrome, X-linked, 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 1, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002283442.1

Allele description [Variation Report for NM_000489.6(ATRX):c.7156C>T (p.Arg2386Ter)]

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

Gene:

ATRX:ATRX chromatin remodeler [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq21.1

Genomic location:

Preferred name:

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

Other names:

R1528*

HGVS:

NC_000023.11:g.77520832G>A
NG_008838.3:g.270438C>T
NM_000489.6:c.7156C>TMANE SELECT
NM_138270.5:c.7042C>T
NP_000480.3:p.Arg2386Ter
NP_612114.2:p.Arg2348Ter
LRG_1153:g.270438C>T
NC_000023.10:g.76776310G>A
NM_000489.4:c.7156C>T

Protein change:

R2348*; ARG1528TER

Links:

OMIM: 300032.0008; dbSNP: rs122445099

NCBI 1000 Genomes Browser:

rs122445099

Molecular consequence:

NM_000489.6:c.7156C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_138270.5:c.7042C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Intellectual disability-hypotonic facies syndrome, X-linked, 1
Synonyms:: XLMR-HYPOTONIC FACIES SYNDROME; Mental retardation-hypotonic facies syndrome X-linked, 1; Smith Fineman Myers syndrome 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010663; MedGen: C4759781; Orphanet: 73220; Orphanet: 93970; Orphanet: 93971; Orphanet: 93972; Orphanet: 93973; Orphanet: 93974; Orphanet: 93975; OMIM: 309580

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002572629	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 1, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 28371217, 7697714, 24690944, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002572629

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 1, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Inherited germline ATRX mutation in two brothers with ATR-X syndrome and osteosarcoma.

Ji J, Quindipan C, Parham D, Shen L, Ruble D, Bootwalla M, Maglinte DT, Gai X, Saitta SC, Biegel JA, Mascarenhas L.

Am J Med Genet A. 2017 May;173(5):1390-1395. doi: 10.1002/ajmg.a.38184. Epub 2017 Mar 28.

PubMed [citation]

PMID:: 28371217
PMCID:: PMC7521841

Mutations in a putative global transcriptional regulator cause X-linked mental retardation with alpha-thalassemia (ATR-X syndrome).

Gibbons RJ, Picketts DJ, Villard L, Higgs DR.

Cell. 1995 Mar 24;80(6):837-45.

PubMed [citation]

PMID:: 7697714

See all PubMed Citations (4)

Details of each submission

From 3billion, SCV002572629.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 1, 2024

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