rs104893667
Positions:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000348.4(SRD5A2):c.78C>T(p.Tyr26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 35)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
SRD5A2
NM_000348.4 synonymous
NM_000348.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.05
Genes affected
SRD5A2 (HGNC:11285): (steroid 5 alpha-reductase 2) This gene encodes a microsomal protein expressed at high levels in androgen-sensitive tissues such as the prostate. The encoded protein is active at acidic pH and is sensitive to the 4-azasteroid inhibitor finasteride. Deficiencies in this gene can result in male pseudohermaphroditism, specifically pseudovaginal perineoscrotal hypospadias (PPSH). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.74).
BP6
?
Variant 2-31580823-G-A is Benign according to our data. Variant chr2-31580823-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2897077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.05 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SRD5A2 | NM_000348.4 | c.78C>T | p.Tyr26= | synonymous_variant | 1/5 | ENST00000622030.2 | |
SRD5A2 | XM_011533072.3 | c.27-47057C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SRD5A2 | ENST00000622030.2 | c.78C>T | p.Tyr26= | synonymous_variant | 1/5 | 1 | NM_000348.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 35
GnomAD3 genomes
?
Cov.:
35
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460158Hom.: 0 Cov.: 37 AF XY: 0.00000138 AC XY: 1AN XY: 726448
GnomAD4 exome
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1
AN:
1460158
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37
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1
AN XY:
726448
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 35
GnomAD4 genome
?
Cov.:
35
Bravo
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2023 | - - |
SRD5A2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 27, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at