rs28383032

Variant names:

• chr2-31536510-G-A
• rs28383032
• NM_000348.4:c.282-2744C>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.282-2744C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 152,150 control chromosomes in the GnomAD database, including 687 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 0.086 (687 hom., cov: 32)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A2	NM_000348.4	c.282-2744C>T		intron_variant	Intron 1 of 4	ENST00000622030.2	NP_000339.2
SRD5A2	XM_011533069.3	c.60-2744C>T		intron_variant	Intron 1 of 4		XP_011531371.1
SRD5A2	XM_011533072.3	c.27-2744C>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.282-2744C>T		intron_variant	Intron 1 of 4	1	NM_000348.4	ENSP00000477587.1
ENSG00000228563	ENST00000435713.1	n.255+8810G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0862 AC: 13107 AN: 152032 Hom.: 686 Cov.: 32

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.0951

Gnomad SAS AF: 0.0973

Gnomad FIN AF: 0.0988

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0862 AC: 13110 AN: 152150 Hom.: 687 Cov.: 32 AF XY: 0.0865 AC XY: 6435 AN XY: 74384

African (AFR) AF: 0.0390 AC: 1618 AN: 41516

American (AMR) AF: 0.0763 AC: 1167 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3468

East Asian (EAS) AF: 0.0949 AC: 490 AN: 5164

South Asian (SAS) AF: 0.0982 AC: 473 AN: 4816

European-Finnish (FIN) AF: 0.0988 AC: 1047 AN: 10592

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7054 AN: 67988

Other (OTH) AF: 0.102 AC: 215 AN: 2114

Alfa AF: 0.0910 Hom.: 93

Bravo AF: 0.0827

Asia WGS AF: 0.0900 AC: 312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.3
DANN	Benign	0.74
PhyloP100		0.38

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: rs28383032; hg19: chr2-31761580;