rs28383018

Variant names:

• chr2-31547411-T-C
• rs28383018
• NM_000348.4:c.282-13645A>G

Variant summary

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

The NM_000348.4(SRD5A2):​c.282-13645A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,086 control chromosomes in the GnomAD database, including 6,780 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 0.27 (6780 hom., cov: 32)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 2 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

ENSG00000228563 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000348.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	NM_000348.4	MANE Select	c.282-13645A>G		intron	N/A	NP_000339.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	ENST00000622030.2	TSL:1 MANE Select	c.282-13645A>G		intron	N/A	ENSP00000477587.1	P31213
	SRD5A2	ENST00000882642.1		c.282-13645A>G		intron	N/A	ENSP00000552701.1
	SRD5A2	ENST00000882643.1		c.282-13645A>G		intron	N/A	ENSP00000552702.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40875 AN: 151968 Hom.: 6784 Cov.: 32

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.351

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.269 AC: 40860 AN: 152086 Hom.: 6780 Cov.: 32 AF XY: 0.273 AC XY: 20323 AN XY: 74332

African (AFR) AF: 0.0674 AC: 2798 AN: 41528

American (AMR) AF: 0.283 AC: 4332 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 1218 AN: 3468

East Asian (EAS) AF: 0.359 AC: 1847 AN: 5140

South Asian (SAS) AF: 0.303 AC: 1460 AN: 4812

European-Finnish (FIN) AF: 0.407 AC: 4304 AN: 10572

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23931 AN: 67962

Other (OTH) AF: 0.279 AC: 589 AN: 2108

Alfa AF: 0.317 Hom.: 1094

Bravo AF: 0.254

Asia WGS AF: 0.254 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.9
DANN	Benign	0.79
PhyloP100		0.15

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: rs28383018; hg19: chr2-31772481;