NM_000348.4(SRD5A2):c.281+2T>C AND 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 21, 2023
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:: RCV003607921.1

Allele description

NM_000348.4(SRD5A2):c.281+2T>C

Gene:

SRD5A2:steroid 5 alpha-reductase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p23.1

Genomic location:

Preferred name:

NM_000348.4(SRD5A2):c.281+2T>C

HGVS:

NC_000002.12:g.31580618A>G
NG_008365.1:g.5354T>C
NG_008365.2:g.87391T>C
NM_000348.4:c.281+2T>CMANE SELECT
NC_000002.11:g.31805688A>G

Molecular consequence:

NM_000348.4:c.281+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency (PPSH)
Synonyms:: Pseudovaginal perineoscrotal hypospadias; Male pseudohermaphroditism due to 5-alpha-reductase deficiency; Familial incomplete male pseudohermaphroditism, type 2; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009923; MedGen: C0268297; Orphanet: 753; OMIM: 264600

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Antigens, Viral
Antigens, Viral
Substances elaborated by viruses that have antigenic activity.<br/>Year introduced: 1973

MeSH
Larva
Larva
Wormlike or grublike stage, following the egg in the life cycle of insects, worms, and other metamorphosing animals.<br/>Year introduced: 1974(1970)

MeSH
Mediastinum
Mediastinum
A membrane in the midline of the THORAX of mammals. It separates the lungs between the STERNUM in front and the VERTEBRAL COLUMN behind. It also surrounds the HEART, TRACHEA, ...<br/>

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004488731	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Mar 21, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 1406794, 1944596, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004488731

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Mar 21, 2023)

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

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

Brief report: the molecular basis of steroid 5 alpha-reductase deficiency in a large Dominican kindred.

Thigpen AE, Davis DL, Gautier T, Imperato-McGinley J, Russell DW.

N Engl J Med. 1992 Oct 22;327(17):1216-9. No abstract available.

PubMed [citation]

PMID:: 1406794

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004488731.1

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with SRD5A2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 1 of the SRD5A2 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 SRD5A2 are known to be pathogenic (PMID: 1406794, 1944596).

#	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: Feb 28, 2024

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