NM_000044.6(AR):c.2225G>A (p.Trp742Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 29, 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:: RCV003802931.2

Allele description [Variation Report for NM_000044.6(AR):c.2225G>A (p.Trp742Ter)]

NM_000044.6(AR):c.2225G>A (p.Trp742Ter)

Gene:

AR:androgen receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq12

Genomic location:

Preferred name:

NM_000044.6(AR):c.2225G>A (p.Trp742Ter)

HGVS:

NC_000023.11:g.67717529G>A
NG_009014.2:g.178498G>A
NM_000044.6:c.2225G>AMANE SELECT
NM_001011645.3:c.629G>A
NM_001424175.1:c.2228G>A
NP_000035.2:p.Trp742Ter
NP_001011645.1:p.Trp210Ter
NP_001411104.1:p.Trp743Ter
LRG_1406t1:c.2225G>A
LRG_1406:g.178498G>A
LRG_1406p1:p.Trp742Ter
NC_000023.10:g.66937371G>A

Protein change:

W210*

Molecular consequence:

NM_000044.6:c.2225G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001011645.3:c.629G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001424175.1:c.2228G>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV004591753	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 29, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 34333495, 19463997, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004591753

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 29, 2022)

germline

clinical testing

PubMed (3)
[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

Clinical, Hormonal, Genetic, and Molecular Characteristics in Androgen Insensitivity Syndrome in an Asian Indian Cohort from a Single Centre in Western India.

Arya S, Barnabas R, Lila AR, Sarathi V, Memon SS, Bhandare VV, Thakkar K, Patil V, Shah NS, Kunwar A, Bandgar T.

Sex Dev. 2021;15(4):253-261. doi: 10.1159/000517763. Epub 2021 Jul 30.

PubMed [citation]

PMID:: 34333495

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004591753.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with androgen insensitivity syndrome (PMID: 34333495). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp742*) 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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