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NM_000348.4(SRD5A2):c.547+1G>C AND 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 31, 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:
RCV003607838.2

Allele description [Variation Report for NM_000348.4(SRD5A2):c.547+1G>C]

NM_000348.4(SRD5A2):c.547+1G>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.547+1G>C
HGVS:
  • NC_000002.12:g.31531370C>G
  • NG_008365.1:g.54602G>C
  • NG_008365.2:g.136639G>C
  • NM_000348.4:c.547+1G>CMANE SELECT
  • NC_000002.11:g.31756440C>G
Molecular consequence:
  • NM_000348.4:c.547+1G>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004410423Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 31, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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 (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004410423.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 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). Disruption of this splice site has been observed in individual(s) with steroid-5 alpha-reductase deficiency (PMID: 15770495). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024