2-31533741-G-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000348.4(SRD5A2):c.307C>T(p.Arg103Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000443 in 1,603,290 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 Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R103R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000348.4 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SRD5A2 | NM_000348.4 | c.307C>T | p.Arg103Ter | stop_gained | 2/5 | ENST00000622030.2 | |
SRD5A2 | XM_011533069.3 | c.85C>T | p.Arg29Ter | stop_gained | 2/5 | ||
SRD5A2 | XM_011533072.3 | c.52C>T | p.Arg18Ter | stop_gained | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SRD5A2 | ENST00000622030.2 | c.307C>T | p.Arg103Ter | stop_gained | 2/5 | 1 | NM_000348.4 | P1 | |
ENST00000435713.1 | n.255+6041G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000215 AC: 5AN: 232538Hom.: 0 AF XY: 0.00000800 AC XY: 1AN XY: 125052
GnomAD4 exome AF: 0.0000441 AC: 64AN: 1451112Hom.: 0 Cov.: 30 AF XY: 0.0000305 AC XY: 22AN XY: 720284
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74346
ClinVar
Submissions by phenotype
3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | 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. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Clinical Genetics and Genomics, Karolinska University Hospital | Jun 05, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at