rs612224

Positions:

• chr2-31586801-C-A
• chr2-31586801-C-G
• chr2-31586801-C-T

Variant summary

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

The XM_011533072.3(SRD5A2):​c.27-53035G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,018 control chromosomes in the GnomAD database, including 40,943 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 0.73 (40943 hom., cov: 31)
• Consequence: SRD5A2 XM_011533072.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRD5A2	XM_011533072.3	c.27-53035G>T		intron_variant			XP_011531374.1
		n.31586801C>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110834 AN: 151900 Hom.: 40889 Cov.: 31

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.728

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.730 AC: 110949 AN: 152018 Hom.: 40943 Cov.: 31 AF XY: 0.727 AC XY: 54054 AN XY: 74308

Gnomad4 AFR AF: 0.833

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.757

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.697

Gnomad4 OTH AF: 0.728

Alfa AF: 0.699 Hom.: 34189

Bravo AF: 0.732

Asia WGS AF: 0.592 AC: 2058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.95
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs612224; hg19: chr2-31811870;