NM_001393392.1(AKR1C2):c.235A>G (p.Ile79Val) AND 46,XY sex reversal 8

Clinical significance:Pathogenic (Last evaluated: Aug 12, 2011)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000022967.2

Allele description [Variation Report for NM_001393392.1(AKR1C2):c.235A>G (p.Ile79Val)]

NM_001393392.1(AKR1C2):c.235A>G (p.Ile79Val)

Gene:
AKR1C2:aldo-keto reductase family 1 member C2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10p15.1
Genomic location:
Preferred name:
NM_001393392.1(AKR1C2):c.235A>G (p.Ile79Val)
HGVS:
  • NC_000010.11:g.5001531T>C
  • NG_031852.1:g.21485A>G
  • NM_001135241.3:c.235A>G
  • NM_001321027.2:c.235A>G
  • NM_001354.6:c.235A>G
  • NM_001393392.1:c.235A>GMANE SELECT
  • NM_205845.3:c.235A>G
  • NP_001128713.1:p.Ile79Val
  • NP_001307956.1:p.Ile79Val
  • NP_001345.1:p.Ile79Val
  • NP_001380321.1:p.Ile79Val
  • NP_995317.1:p.Ile79Val
  • NC_000010.10:g.5043723T>C
  • P52895:p.Ile79Val
Protein change:
I79V; ILE79VAL
Links:
UniProtKB: P52895#VAR_066632; OMIM: 600450.0001; dbSNP: rs387906750
NCBI 1000 Genomes Browser:
rs387906750
Molecular consequence:
  • NM_001135241.3:c.235A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001321027.2:c.235A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354.6:c.235A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001393392.1:c.235A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_205845.3:c.235A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
46,XY sex reversal 8 (SRXY8)
Synonyms:
MALE PSEUDOHERMAPHRODITISM DUE TO DEFICIENCY OF TESTICULAR 17,20-DESMOLASE; 46,XY SEX REVERSAL 8, MODIFIER OF
Identifiers:
Gene: 6994; MONDO: MONDO:0013664; MedGen: C1839840; OMIM: 614279

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000044258OMIMno assertion criteria providedPathogenic
(Aug 12, 2011)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Steroid 17,20-desmolase deficiency: a new cause of male pseudohermaphroditism.

Zachmann M, Völlmin JA, Hamilton W, Prader A.

Clin Endocrinol (Oxf). 1972 Oct;1(4):369-85. No abstract available.

PubMed [citation]
PMID:
4352099

Why boys will be boys: two pathways of fetal testicular androgen biosynthesis are needed for male sexual differentiation.

Flück CE, Meyer-Böni M, Pandey AV, Kempná P, Miller WL, Schoenle EJ, Biason-Lauber A.

Am J Hum Genet. 2011 Aug 12;89(2):201-18. doi: 10.1016/j.ajhg.2011.06.009. Epub 2011 Jul 28. Erratum in: Am J Hum Genet. 2011 Aug 12;89(2):347.

PubMed [citation]
PMID:
21802064
PMCID:
PMC3155178

Details of each submission

From OMIM, SCV000044258.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a Swiss family with 46,XY sex reversal (SRXY8; 614279) originally studied by Zachmann et al. (1972), Fluck et al. (2011) identified 3 different missense mutations in the AKR1C2 gene: a 235A-G transition in exon 5, resulting in an ile79-to-val (I79V) substitution; a 270T-G transversion in exon 6, resulting in a his90-to-gln (H90Q; 600450.0002) substitution; and an 899A-C transversion in exon 10, resulting in asn300-to-thr (N300T; 600450.0003). None of the 3 mutations was found in 200 controls, and all 3 demonstrated reduced activity compared to wildtype in functional assays. The maternal 46,XY aunt of the 2 originally studied affected male cousins was compound heterozygous for the I79V and H90Q mutations, whereas 1 of the 2 male cousins was heterozygous for I79V; the second male cousin declined genetic testing, but his 46,XY sister was compound heterozygous for I79V and N300T, and a phenotypically normal 46,XX sister carried the H90Q mutation. Fluck et al. (2011) observed that all affected individuals had a 46,XY karyotype: a 46,XX sister of the 46,XY aunt was compound heterozygous for the same 2 AKR1C2 mutations, I79V and H90Q, but was phenotypically normal and had borne 3 children, and another phenotypically normal 46,XX sister was heterozygous for the same I79V mutation in AKR1C2 carried by her moderately affected son. The 46,XY phenotypically normal father of the 3 children also carried a heterozygous mutation in AKR1C2, N300T. Fluck et al. (2011) also identified a splice site mutation in the AKR1C4 gene (600451.0001) that segregated with the I79V mutation all cases. The authors stated that their findings suggested a mode of inheritance in which the severity of the developmental defect depended on the number of mutations in the 2 genes in a given individual.

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

Last Updated: Oct 25, 2021

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