chr2-31554334-T-A

Variant names:

• chr2-31554334-T-A
• rs2268794
• NM_000348.4:c.282-20568A>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.282-20568A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,134 control chromosomes in the GnomAD database, including 3,585 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 0.19 (3585 hom., cov: 32)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171
• Publications: 9 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

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 (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A2	NM_000348.4	c.282-20568A>T		intron_variant	Intron 1 of 4	ENST00000622030.2	NP_000339.2
SRD5A2	XM_011533069.3	c.59+4119A>T		intron_variant	Intron 1 of 4		XP_011531371.1
SRD5A2	XM_011533072.3	c.27-20568A>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.282-20568A>T		intron_variant	Intron 1 of 4	1	NM_000348.4	ENSP00000477587.1
ENSG00000228563	ENST00000435713.1	n.256-8740T>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29197 AN: 152016 Hom.: 3565 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.192 AC: 29257 AN: 152134 Hom.: 3585 Cov.: 32 AF XY: 0.189 AC XY: 14070 AN XY: 74372

African (AFR) AF: 0.351 AC: 14580 AN: 41482

American (AMR) AF: 0.119 AC: 1823 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 960 AN: 3470

East Asian (EAS) AF: 0.104 AC: 537 AN: 5182

South Asian (SAS) AF: 0.147 AC: 711 AN: 4822

European-Finnish (FIN) AF: 0.132 AC: 1394 AN: 10584

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8679 AN: 67990

Other (OTH) AF: 0.184 AC: 389 AN: 2110

Alfa AF: 0.168 Hom.: 354

Bravo AF: 0.198

Asia WGS AF: 0.135 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.71
PhyloP100		-0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2268794; hg19: chr2-31779404;