2-31578786-GT-GTT

Position:

• chr2-31578786-GT-GTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000348.4(SRD5A2):​c.281+1833dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 151,192 control chromosomes in the GnomAD database, including 1,403 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1403 hom., cov: 30)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRD5A2	NM_000348.4	c.281+1833dupA		intron_variant		ENST00000622030.2	NP_000339.2
SRD5A2	XM_011533072.3	c.27-45021dupA		intron_variant			XP_011531374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRD5A2	ENST00000622030.2	c.281+1833dupA		intron_variant		1	NM_000348.4	ENSP00000477587.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19497 AN: 151076 Hom.: 1400 Cov.: 30

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.0808

Gnomad AMR AF: 0.0942

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0992

Gnomad FIN AF: 0.0991

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.129 AC: 19519 AN: 151192 Hom.: 1403 Cov.: 30 AF XY: 0.129 AC XY: 9491 AN XY: 73832

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.0941

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0997

Gnomad4 FIN AF: 0.0991

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.135

Asia WGS AF: 0.102 AC: 354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs28382999; hg19: chr2-31803856;