NM_000044.6(AR):c.1885+2T>G AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 4, 2021
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:: RCV001946527.4

Allele description [Variation Report for NM_000044.6(AR):c.1885+2T>G]

NM_000044.6(AR):c.1885+2T>G

Gene:

AR:androgen receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq12

Genomic location:

Preferred name:

NM_000044.6(AR):c.1885+2T>G

HGVS:

NC_000023.11:g.67686128T>G
NG_009014.2:g.147097T>G
NM_000044.6:c.1885+2T>GMANE SELECT
NM_001011645.3:c.289+2T>G
NM_001348061.1:c.1885+2T>G
NM_001348063.1:c.1885+2T>G
NM_001348064.1:c.*83+2T>G
LRG_1406t1:c.1885+2T>G
LRG_1406:g.147097T>G
NC_000023.10:g.66905970T>G

Links:

dbSNP: rs2147497993

NCBI 1000 Genomes Browser:

rs2147497993

Molecular consequence:

NM_000044.6:c.1885+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001011645.3:c.289+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001348061.1:c.1885+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001348063.1:c.1885+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001348064.1:c.*83+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Androgen resistance syndrome (AIS)
Synonyms:: TESTICULAR FEMINIZATION SYNDROME; Androgen insensitivity syndrome; Androgen receptor deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0019154; MedGen: C0039585; Orphanet: 99429; OMIM: 300068

Name:: Kennedy disease (SMAX1)
Synonyms:: SPINAL AND BULBAR MUSCULAR ATROPHY, X-LINKED 1; Bulbo-spinal atrophy X-linked; Kennedy spinal and bulbar muscular atrophy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010735; MedGen: C1839259; Orphanet: 481; OMIM: 313200

Recent activity

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CBTC5947.fwd NICHD_XGC_tropBone1 Xenopus tropicalis cDNA clone IMAGE:8938201 5',...
CBTC5947.fwd NICHD_XGC_tropBone1 Xenopus tropicalis cDNA clone IMAGE:8938201 5', mRNA sequence
gi|126268062|gnl|dbEST|45041889|gb| 337.1|

Nucleotide
JGI_CAAO1496.rev NIH_XGC_tropTe5 Xenopus tropicalis cDNA clone IMAGE:7698688 3',...
JGI_CAAO1496.rev NIH_XGC_tropTe5 Xenopus tropicalis cDNA clone IMAGE:7698688 3', mRNA sequence
gi|71934402|gnl|dbEST|30597730|gb|C 29.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002214546	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 4, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 22334387, 16199547, 19463997, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002214546

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 4, 2021)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The androgen receptor gene mutations database: 2012 update.

Gottlieb B, Beitel LK, Nadarajah A, Paliouras M, Trifiro M.

Hum Mutat. 2012 May;33(5):887-94. doi: 10.1002/humu.22046. Epub 2012 Mar 13.

PubMed [citation]

PMID:: 22334387

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002214546.3

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

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individual(s) with complete androgen insensitivity syndrome (PMID: 22334387). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 of the AR gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in AR are known to be pathogenic (PMID: 19463997).

#	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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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