rs12470143

Variant names:

• chr2-31538488-C-T
• rs12470143
• NM_000348.4:c.282-4722G>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.282-4722G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 151,954 control chromosomes in the GnomAD database, including 13,663 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 0.42 (13663 hom., cov: 32)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 19 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 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.282-4722G>A		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.282-4722G>A		intron	N/A	ENSP00000477587.1	P31213
	SRD5A2	ENST00000882642.1		c.282-4722G>A		intron	N/A	ENSP00000552701.1
	SRD5A2	ENST00000882643.1		c.282-4722G>A		intron	N/A	ENSP00000552702.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63312 AN: 151836 Hom.: 13664 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.417 AC: 63328 AN: 151954 Hom.: 13663 Cov.: 32 AF XY: 0.419 AC XY: 31116 AN XY: 74274

African (AFR) AF: 0.308 AC: 12769 AN: 41416

American (AMR) AF: 0.458 AC: 7001 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1386 AN: 3470

East Asian (EAS) AF: 0.353 AC: 1820 AN: 5162

South Asian (SAS) AF: 0.358 AC: 1724 AN: 4818

European-Finnish (FIN) AF: 0.501 AC: 5295 AN: 10560

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.470 AC: 31933 AN: 67938

Other (OTH) AF: 0.410 AC: 866 AN: 2112

Alfa AF: 0.450 Hom.: 66015

Bravo AF: 0.410

Asia WGS AF: 0.305 AC: 1062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.88
DANN	Benign	0.74
PhyloP100		-0.13

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: rs12470143; hg19: chr2-31763558;