NM_000044.6(AR):c.830_845dup (p.Pro283fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 18, 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:: RCV000700147.5

Allele description [Variation Report for NM_000044.6(AR):c.830_845dup (p.Pro283fs)]

NM_000044.6(AR):c.830_845dup (p.Pro283fs)

Gene:

AR:androgen receptor [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

Xq12

Genomic location:

Preferred name:

NM_000044.6(AR):c.830_845dup (p.Pro283fs)

HGVS:

NC_000023.11:g.67545976_67545991dup
NG_009014.2:g.6945_6960dup
NM_000044.6:c.830_845dupMANE SELECT
NM_001011645.3:c.-954_-939dup
NM_001348061.1:c.830_845dup
NM_001348063.1:c.830_845dup
NM_001348064.1:c.830_845dup
NP_000035.2:p.Pro283fs
NP_001334990.1:p.Pro283fs
NP_001334992.1:p.Pro283fs
NP_001334993.1:p.Pro283fs
LRG_1406t1:c.830_845dup
LRG_1406:g.6945_6960dup
LRG_1406p1:p.Pro283fs
NC_000023.10:g.66765813_66765814insCCACCCGCTGTGCGTC
NC_000023.10:g.66765818_66765833dup
NM_000044.3:c.830_845dup

Protein change:

P283fs

Links:

dbSNP: rs1569264288

NCBI 1000 Genomes Browser:

rs1569264288

Molecular consequence:

NM_001011645.3:c.-954_-939dup - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000044.6:c.830_845dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001348061.1:c.830_845dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001348063.1:c.830_845dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001348064.1:c.830_845dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000828891	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 18, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19463997, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000828891

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 18, 2021)

germline

clinical testing

PubMed (2)
[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

Complete androgen insensitivity syndrome is frequently due to premature stop codons in exon 1 of the androgen receptor gene: an international collaborative report of 13 new mutations.

Philibert P, Audran F, Pienkowski C, Morange I, Kohler B, Flori E, Heinrich C, Dacou-Voutetakis C, Joseph MG, Guedj AM, Journel H, Hecart-Bruna AC, Khotchali I, Ten S, Bouchard P, Paris F, Sultan C.

Fertil Steril. 2010 Jul;94(2):472-6. doi: 10.1016/j.fertnstert.2009.03.057. Epub 2009 May 21.

PubMed [citation]

PMID:: 19463997

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000828891.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 577402). This variant has not been reported in the literature in individuals affected with AR-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro283Argfs*27) in the AR gene. It is expected to result in an absent or disrupted protein product. 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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