2-31525043-TAA-TAAA

Variant names:

• chr2-31525043-T-TA
• rs74702388
• NM_000348.4:c.*1152dupT

Variant summary

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

The NM_000348.4(SRD5A2):​c.*1152dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (26 hom., cov: 32)
  • Exomes 𝑓: 0.37 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: SRD5A2 NM_000348.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414

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: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A2	NM_000348.4	c.*1152dupT		3_prime_UTR_variant	Exon 5 of 5	ENST00000622030.2	NP_000339.2
SRD5A2	XM_011533069.3	c.*1152dupT		3_prime_UTR_variant	Exon 5 of 5		XP_011531371.1
SRD5A2	XM_011533072.3	c.*1152dupT		3_prime_UTR_variant	Exon 7 of 7		XP_011531374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SRD5A2	ENST00000622030	c.*1152dupT		3_prime_UTR_variant	Exon 5 of 5	1	NM_000348.4	ENSP00000477587.1

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2708 AN: 140766 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.0426

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.00879

Gnomad EAS AF: 0.00344

Gnomad SAS AF: 0.00540

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.00671

Gnomad NFE AF: 0.0187

Gnomad OTH AF: 0.0205

GnomAD4 exome AF: 0.371 AC: 16522 AN: 44474 Hom.: 1 Cov.: 0 AF XY: 0.372 AC XY: 7673 AN XY: 20618

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.343

Gnomad4 ASJ exome AF: 0.384

Gnomad4 EAS exome AF: 0.390

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.366

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0193 AC: 2723 AN: 140812 Hom.: 26 Cov.: 32 AF XY: 0.0190 AC XY: 1297 AN XY: 68192

Gnomad4 AFR AF: 0.0200

Gnomad4 AMR AF: 0.0155

Gnomad4 ASJ AF: 0.00879

Gnomad4 EAS AF: 0.00345

Gnomad4 SAS AF: 0.00564

Gnomad4 FIN AF: 0.0458

Gnomad4 NFE AF: 0.0187

Gnomad4 OTH AF: 0.0220

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: rs74702388; hg19: chr2-31750113;