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: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia

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.

Variant Effect in Transcripts

 

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

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 v4.9

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;