2-31532485-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000348.4(SRD5A2):c.446-1013T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,884 control chromosomes in the GnomAD database, including 1,708 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 0.14 (1708 hom., cov: 31)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.977

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A2	NM_000348.4	c.446-1013T>C		intron_variant		ENST00000622030.2
SRD5A2	XM_011533069.3	c.224-1013T>C		intron_variant
SRD5A2	XM_011533072.3	c.191-1013T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A2	ENST00000622030.2	c.446-1013T>C		intron_variant		1	NM_000348.4	P1
	ENST00000435713.1	n.255+4785A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21825 AN: 151764 Hom.: 1697 Cov.: 31

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.144 AC: 21869 AN: 151884 Hom.: 1708 Cov.: 31 AF XY: 0.143 AC XY: 10595 AN XY: 74256

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0593 Hom.: 69

Bravo AF: 0.146

Asia WGS AF: 0.133 AC: 461 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.21
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7571644; hg19: chr2-31757555;