rs3731586

Positions:

• chr2-31523958-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000348.4(SRD5A2):​c.*2238A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 217,676 control chromosomes in the GnomAD database, including 2,167 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.13 (1504 hom., cov: 32)
  • Exomes 𝑓: 0.13 (663 hom.)
• Consequence: SRD5A2 NM_000348.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.804

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A2	NM_000348.4	c.*2238A>G		3_prime_UTR_variant	5/5	ENST00000622030.2
SRD5A2	XM_011533069.3	c.*2238A>G		3_prime_UTR_variant	5/5
SRD5A2	XM_011533072.3	c.*2238A>G		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A2	ENST00000622030.2	c.*2238A>G		3_prime_UTR_variant	5/5	1	NM_000348.4	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20244 AN: 152090 Hom.: 1494 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.0953

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0982

Gnomad FIN AF: 0.0990

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.129 AC: 8467 AN: 65466 Hom.: 663 Cov.: 0 AF XY: 0.131 AC XY: 3976 AN XY: 30390

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.0983

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.0915

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.109

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.133 AC: 20287 AN: 152210 Hom.: 1504 Cov.: 32 AF XY: 0.132 AC XY: 9799 AN XY: 74416

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.0953

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0989

Gnomad4 FIN AF: 0.0990

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.132

Alfa AF: 0.115 Hom.: 420

Bravo AF: 0.138

Asia WGS AF: 0.106 AC: 367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3731586; hg19: chr2-31749028;