NM_000489.6(ATRX):c.536A>G (p.Asn179Ser) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 2, 2016
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000078965.8

Allele description [Variation Report for NM_000489.6(ATRX):c.536A>G (p.Asn179Ser)]

NM_000489.6(ATRX):c.536A>G (p.Asn179Ser)

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.536A>G (p.Asn179Ser)

Other names:

NM_000489.5(ATRX):c.536A>G

HGVS:

NC_000023.11:g.77688876T>C
NG_008838.3:g.102394A>G
NM_000489.6:c.536A>GMANE SELECT
NM_138270.5:c.422A>G
NP_000480.3:p.Asn179Ser
NP_612114.2:p.Asn141Ser
LRG_1153:g.102394A>G
NC_000023.10:g.76944369T>C
NM_000489.3:c.536A>G
NM_000489.4:c.536A>G
NP_000480.2:p.Asn179Ser

Protein change:

N141S

Links:

dbSNP: rs398123425

NCBI 1000 Genomes Browser:

rs398123425

Molecular consequence:

NM_000489.6:c.536A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_138270.5:c.422A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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gi|1731019115|gb|TYK06920.1||gnl|WG D|E5676_scaffold13G002300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000110830	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Feb 3, 2014)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10995512, 16813605, 18409179, 8968741, 9244431 Citation Link,
SCV000520865	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jun 2, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000110830

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Feb 3, 2014)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link,

SCV000520865

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jun 2, 2016)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	6	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular genetic study of japanese patients with X-linked alpha-thalassemia/mental retardation syndrome (ATR-X).

Wada T, Kubota T, Fukushima Y, Saitoh S.

Am J Med Genet. 2000 Sep 18;94(3):242-8.

PubMed [citation]

PMID:: 10995512

Mutations in PHD-like domain of the ATRX gene correlate with severe psychomotor impairment and severe urogenital abnormalities in patients with ATRX syndrome.

Badens C, Lacoste C, Philip N, Martini N, Courrier S, Giuliano F, Verloes A, Munnich A, Leheup B, Burglen L, Odent S, Van Esch H, Levy N.

Clin Genet. 2006 Jul;70(1):57-62.

PubMed [citation]

PMID:: 16813605

See all PubMed Citations (5)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000110830.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	6	not provided	not provided	clinical testing	PubMed (5)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		6	not provided	not provided	not provided

From GeneDx, SCV000520865.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The c.536 A>G pathogenic variant in the ATRX gene has been reported previously in association with ATRX-related disorders (Picketts et al., 1996; Badens et al., 2006; Wada et al., 2000). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Functional studies indicate that c.536 A>G creates a cryptic splice donor site, leading to a deletion of 63 nucleotides (reported as A751G using alternate nomenclature in Villard et al., 1997; reported as A869G using alternate nomenclature in Picketts et al., 1996). This substitution occurs in the ADD domain and pathogenic variants affecting this domain are presumed to have structural consequences on the ATRX protein and impact histone methylation (Argentaro et al., 2007; Iwase et al., 2011; Stenson et al., 2014).

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

Last Updated: Oct 13, 2024

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