rs2208532

Variant names:

• chr2-31563919-G-A
• rs2208532
• NM_000348.4:c.281+16701C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-31563919-G-A
• chr2-31563919-G-T

Variant summary

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

The NM_000348.4(SRD5A2):​c.281+16701C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,762 control chromosomes in the GnomAD database, including 26,604 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 0.59 (26604 hom., cov: 31)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 17 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A2	NM_000348.4	c.281+16701C>T		intron_variant	Intron 1 of 4	ENST00000622030.2	NP_000339.2
SRD5A2	XM_011533072.3	c.27-30153C>T		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.281+16701C>T		intron_variant	Intron 1 of 4	1	NM_000348.4	ENSP00000477587.1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89148 AN: 151644 Hom.: 26577 Cov.: 31

Gnomad AFR AF: 0.669

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.588 AC: 89217 AN: 151762 Hom.: 26604 Cov.: 31 AF XY: 0.588 AC XY: 43599 AN XY: 74162

African (AFR) AF: 0.669 AC: 27720 AN: 41432

American (AMR) AF: 0.543 AC: 8264 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2323 AN: 3462

East Asian (EAS) AF: 0.446 AC: 2304 AN: 5164

South Asian (SAS) AF: 0.483 AC: 2325 AN: 4814

European-Finnish (FIN) AF: 0.606 AC: 6399 AN: 10552

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 37979 AN: 67806

Other (OTH) AF: 0.570 AC: 1196 AN: 2098

Alfa AF: 0.555 Hom.: 12093

Bravo AF: 0.586

Asia WGS AF: 0.434 AC: 1509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.41
PhyloP100		-0.031

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: rs2208532; hg19: chr2-31788989;