rs2268797

Variant names:

• chr2-31558682-C-T
• rs2268797
• NM_000348.4:c.281+21938G>A

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+21938G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,978 control chromosomes in the GnomAD database, including 20,411 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 0.51 (20411 hom., cov: 32)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A2	NM_000348.4	c.281+21938G>A		intron_variant	Intron 1 of 4	ENST00000622030.2	NP_000339.2
SRD5A2	XM_011533069.3	c.-171G>A		5_prime_UTR_variant	Exon 1 of 5		XP_011531371.1
SRD5A2	XM_011533072.3	c.27-24916G>A		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+21938G>A		intron_variant	Intron 1 of 4	1	NM_000348.4	ENSP00000477587.1
ENSG00000228563	ENST00000435713.1	n.256-4392C>T		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77602 AN: 151860 Hom.: 20411 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.511 AC: 77629 AN: 151978 Hom.: 20411 Cov.: 32 AF XY: 0.512 AC XY: 38026 AN XY: 74256

African (AFR) AF: 0.396 AC: 16384 AN: 41424

American (AMR) AF: 0.549 AC: 8389 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1670 AN: 3466

East Asian (EAS) AF: 0.377 AC: 1944 AN: 5162

South Asian (SAS) AF: 0.460 AC: 2215 AN: 4810

European-Finnish (FIN) AF: 0.573 AC: 6051 AN: 10554

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.576 AC: 39185 AN: 67972

Other (OTH) AF: 0.519 AC: 1093 AN: 2106

Alfa AF: 0.534 Hom.: 2885

Bravo AF: 0.503

Asia WGS AF: 0.370 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.5
DANN	Benign	0.64
PhyloP100		0.30

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: rs2268797; hg19: chr2-31783752;