NM_000348.4(SRD5A2):c.169G>C (p.Glu57Gln) AND 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 25, 2020
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:: RCV000582093.6

Allele description [Variation Report for NM_000348.4(SRD5A2):c.169G>C (p.Glu57Gln)]

NM_000348.4(SRD5A2):c.169G>C (p.Glu57Gln)

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.169G>C (p.Glu57Gln)

HGVS:

NC_000002.12:g.31580732C>G
NG_008365.1:g.5240G>C
NM_000348.4:c.169G>CMANE SELECT
NP_000339.2:p.Glu57Gln
NC_000002.11:g.31805802C>G
NM_000348.3:c.169G>C

Protein change:

E57Q

Links:

dbSNP: rs750444774

NCBI 1000 Genomes Browser:

rs750444774

Molecular consequence:

NM_000348.4:c.169G>C - missense variant - [Sequence Ontology: SO:0001583]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000692379	Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	no assertion criteria provided	Pathogenic (Sep 23, 2013)	germline	clinical testing
SCV002231149	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 25, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21147889, 18350250, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000692379

Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital

no assertion criteria provided

Pathogenic
(Sep 23, 2013)

germline

clinical testing

SCV002231149

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 25, 2020)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Phenotypical, biological, and molecular heterogeneity of 5α-reductase deficiency: an extensive international experience of 55 patients.

Maimoun L, Philibert P, Cammas B, Audran F, Bouchard P, Fenichel P, Cartigny M, Pienkowski C, Polak M, Skordis N, Mazen I, Ocal G, Berberoglu M, Reynaud R, Baumann C, Cabrol S, Simon D, Kayemba-Kay's K, De Kerdanet M, Kurtz F, Leheup B, Heinrichs C, et al.

J Clin Endocrinol Metab. 2011 Feb;96(2):296-307. doi: 10.1210/jc.2010-1024. Epub 2010 Dec 8.

PubMed [citation]

PMID:: 21147889

Novel compound heterozygous mutations in the SRD5A2 gene from 46,XY infants with ambiguous external genitalia.

Vilchis F, Valdez E, Ramos L, García R, Gómez R, Chávez B.

J Hum Genet. 2008;53(5):401-406. doi: 10.1007/s10038-008-0274-2. Epub 2008 Mar 19.

PubMed [citation]

PMID:: 18350250

See all PubMed Citations (3)

Details of each submission

From Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital, SCV000692379.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002231149.2

#	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. Experimental studies have shown that this variant affects SRD5A2 protein function (PMID: 18350250). This variant has been observed in individual(s) with steroid-5 alpha-reductase deficiency (PMID: 21147889, 18350250). ClinVar contains an entry for this variant (Variation ID: 492896). This variant is present in population databases (rs750444774, ExAC 0.01%). This sequence change replaces glutamic acid with glutamine at codon 57 of the SRD5A2 protein (p.Glu57Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine.

#	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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