NM_000348.4(SRD5A2):c.307C>T (p.Arg103Ter) AND 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 11, 2024
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:: RCV000634579.7

Allele description [Variation Report for NM_000348.4(SRD5A2):c.307C>T (p.Arg103Ter)]

NM_000348.4(SRD5A2):c.307C>T (p.Arg103Ter)

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.307C>T (p.Arg103Ter)

HGVS:

NC_000002.12:g.31533741G>A
NG_008365.1:g.52231C>T
NM_000348.4:c.307C>TMANE SELECT
NP_000339.2:p.Arg103Ter
NC_000002.10:g.31612315G>A
NC_000002.11:g.31758811G>A
NM_000348.3:c.307C>T

Protein change:

R103*

Links:

dbSNP: rs267599353

NCBI 1000 Genomes Browser:

rs267599353

Molecular consequence:

NM_000348.4:c.307C>T - nonsense - [Sequence Ontology: SO:0001587]

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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Chain J, 28S ribosomal protein S12, mitochondrial
Chain J, 28S ribosomal protein S12, mitochondrial
gi|2413506457|pdb|8CSU|J

Protein
Chain Z, 28S ribosomal protein S33, mitochondrial
Chain Z, 28S ribosomal protein S33, mitochondrial
gi|2413506473|pdb|8CSU|Z

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000755909	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 11, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 1406794, 1944596, 11869378, 22876553, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000755909

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 11, 2024)

germline

clinical testing

PubMed (5)
[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

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

Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism.

Andersson S, Berman DM, Jenkins EP, Russell DW.

Nature. 1991 Nov 14;354(6349):159-61.

PubMed [citation]

PMID:: 1944596
PMCID:: PMC4451825

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000755909.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Arg103*) in the SRD5A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SRD5A2 are known to be pathogenic (PMID: 1406794, 1944596). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with steroid-5 alpha-reductase deficiency (PMID: 11869378, 22876553). ClinVar contains an entry for this variant (Variation ID: 74593). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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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