rs4952222

Variant names:

• chr2-31574793-C-A
• rs4952222
• NM_000348.4:c.281+5827G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-31574793-C-A
• chr2-31574793-C-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.281+5827G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 152,314 control chromosomes in the GnomAD database, including 265 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 0.048 (265 hom., cov: 33)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A2	NM_000348.4	c.281+5827G>T		intron_variant	Intron 1 of 4	ENST00000622030.2	NP_000339.2
SRD5A2	XM_011533072.3	c.27-41027G>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.281+5827G>T		intron_variant	Intron 1 of 4	1	NM_000348.4	ENSP00000477587.1

Frequencies

GnomAD3 genomes AF: 0.0478 AC: 7274 AN: 152196 Hom.: 261 Cov.: 33

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.0201

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0547

Gnomad OTH AF: 0.0469

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

GnomAD4 genome AF: 0.0478 AC: 7286 AN: 152314 Hom.: 265 Cov.: 33 AF XY: 0.0475 AC XY: 3541 AN XY: 74472

African (AFR) AF: 0.0241 AC: 1000 AN: 41578

American (AMR) AF: 0.123 AC: 1876 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0216 AC: 75 AN: 3472

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5186

South Asian (SAS) AF: 0.0386 AC: 186 AN: 4824

European-Finnish (FIN) AF: 0.0201 AC: 213 AN: 10614

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0548 AC: 3725 AN: 68024

Other (OTH) AF: 0.0479 AC: 101 AN: 2110

Alfa AF: 0.0339 Hom.: 38

Bravo AF: 0.0528

Asia WGS AF: 0.0330 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.39
PhyloP100		-0.012

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: rs4952222; hg19: chr2-31799863;