2-31583901-T-C

Variant names:

• chr2-31583901-T-C
• rs676033
• XM_011533072.3:c.27-50135A>G

Variant summary

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

The XM_011533072.3(SRD5A2):​c.27-50135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 151,688 control chromosomes in the GnomAD database, including 35,813 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 0.69 (35813 hom., cov: 29)
• Consequence: SRD5A2 XM_011533072.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.33
• Publications: 6 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A2	XM_011533072.3	c.27-50135A>G		intron_variant	Intron 3 of 6		XP_011531374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.686 AC: 103909 AN: 151566 Hom.: 35799 Cov.: 29

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.685 AC: 103967 AN: 151688 Hom.: 35813 Cov.: 29 AF XY: 0.685 AC XY: 50732 AN XY: 74104

African (AFR) AF: 0.690 AC: 28556 AN: 41358

American (AMR) AF: 0.670 AC: 10225 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.754 AC: 2615 AN: 3466

East Asian (EAS) AF: 0.492 AC: 2510 AN: 5104

South Asian (SAS) AF: 0.622 AC: 2972 AN: 4776

European-Finnish (FIN) AF: 0.690 AC: 7246 AN: 10494

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47504 AN: 67920

Other (OTH) AF: 0.695 AC: 1464 AN: 2106

Alfa AF: 0.692 Hom.: 4736

Bravo AF: 0.682

Asia WGS AF: 0.523 AC: 1820 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.61
PhyloP100		-2.3

Splicing

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

Other links and lift over

dbSNP: rs676033; hg19: chr2-31808970;