rs4952220

chr2-31540486-C-Achr2-31540486-C-Gchr2-31540486-C-T

Variant summary

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

The NM_000348.4(SRD5A2):c.282-6720G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,768 control chromosomes in the GnomAD database, including 20,883 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 0.52 (20883 hom., cov: 32)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474

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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A2	NM_000348.4	c.282-6720G>T		intron_variant		ENST00000622030.2
SRD5A2	XM_011533069.3	c.60-6720G>T		intron_variant
SRD5A2	XM_011533072.3	c.27-6720G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A2	ENST00000622030.2	c.282-6720G>T		intron_variant		1	NM_000348.4	P1
	ENST00000435713.1	n.255+12786C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.521 AC: 78963 AN: 151650 Hom.: 20886 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.520 AC: 78986 AN: 151768 Hom.: 20883 Cov.: 32 AF XY: 0.523 AC XY: 38776 AN XY: 74166

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.530

Alfa AF: 0.549 Hom.: 28755

Bravo AF: 0.513

Asia WGS AF: 0.384 AC: 1336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.60
Dann	Benign	0.16

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

Publications

LitVar

Other links and lift over

dbSNP: rs4952220; hg19: chr2-31765556;