NM_000348.4:c.281+2287A>G

Variant names:

• chr2-31578333-T-C
• rs2754530
• NM_000348.4:c.281+2287A>G

Variant summary

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

The NM_000348.4(SRD5A2):​c.281+2287A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 150,668 control chromosomes in the GnomAD database, including 31,280 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 0.64 (31280 hom., cov: 32)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A2	NM_000348.4	c.281+2287A>G		intron_variant	Intron 1 of 4	ENST00000622030.2	NP_000339.2
SRD5A2	XM_011533072.3	c.27-44567A>G		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+2287A>G		intron_variant	Intron 1 of 4	1	NM_000348.4	ENSP00000477587.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 96913 AN: 150560 Hom.: 31274 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.644 AC: 96958 AN: 150668 Hom.: 31280 Cov.: 32 AF XY: 0.646 AC XY: 47495 AN XY: 73540

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.756

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.667

Alfa AF: 0.676 Hom.: 50994

Bravo AF: 0.632

Asia WGS AF: 0.487 AC: 1696 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	3.3
DANN	Benign	0.35

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: rs2754530; hg19: chr2-31803403;