rs725631

Variant names:

• chr2-31555956-A-C
• rs725631
• NM_000348.4:c.282-22190T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000348.4(SRD5A2):​c.282-22190T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 151,998 control chromosomes in the GnomAD database, including 40,053 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 0.72 (40053 hom., cov: 31)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.939
• Publications: 4 publications found

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]

SRD5A2 Gene-Disease associations (from GenCC):

• 46,XY disorder of sex development due to 5-alpha-reductase 2 deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000228563 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A2	NM_000348.4	c.282-22190T>G		intron_variant	Intron 1 of 4	ENST00000622030.2	NP_000339.2
SRD5A2	XM_011533069.3	c.59+2497T>G		intron_variant	Intron 1 of 4		XP_011531371.1
SRD5A2	XM_011533072.3	c.27-22190T>G		intron_variant	Intron 3 of 6		XP_011531374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A2	ENST00000622030.2	c.282-22190T>G		intron_variant	Intron 1 of 4	1	NM_000348.4	ENSP00000477587.1
ENSG00000228563	ENST00000435713.1	n.256-7118A>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109715 AN: 151880 Hom.: 40010 Cov.: 31

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.722 AC: 109811 AN: 151998 Hom.: 40053 Cov.: 31 AF XY: 0.721 AC XY: 53550 AN XY: 74272

African (AFR) AF: 0.796 AC: 33023 AN: 41474

American (AMR) AF: 0.687 AC: 10492 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2666 AN: 3470

East Asian (EAS) AF: 0.493 AC: 2540 AN: 5156

South Asian (SAS) AF: 0.624 AC: 3013 AN: 4826

European-Finnish (FIN) AF: 0.707 AC: 7462 AN: 10548

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48182 AN: 67944

Other (OTH) AF: 0.729 AC: 1535 AN: 2106

Alfa AF: 0.720 Hom.: 4925

Bravo AF: 0.723

Asia WGS AF: 0.525 AC: 1828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		-0.94

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

Other links and lift over

dbSNP: rs725631; hg19: chr2-31781026;