2-31527787-T-G

Variant names:

• chr2-31527787-T-G
• rs11889731
• NM_000348.4:c.698+1520A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000348.4(SRD5A2):​c.698+1520A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,234 control chromosomes in the GnomAD database, including 1,931 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 0.15 (1930 hom., cov: 32)
  • Exomes 𝑓: 0.19 (1 hom.)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000348.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	NM_000348.4	MANE Select	c.698+1520A>C		intron	N/A	NP_000339.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	ENST00000622030.2	TSL:1 MANE Select	c.698+1520A>C		intron	N/A	ENSP00000477587.1
	ENSG00000228563	ENST00000435713.1	TSL:3	n.255+87T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23334 AN: 152100 Hom.: 1915 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.188 AC: 3 AN: 16 Hom.: 1 AF XY: 0.200 AC XY: 2 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 3 AN: 12

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.154 AC: 23384 AN: 152218 Hom.: 1930 Cov.: 32 AF XY: 0.152 AC XY: 11299 AN XY: 74426

African (AFR) AF: 0.213 AC: 8837 AN: 41506

American (AMR) AF: 0.107 AC: 1643 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 963 AN: 3470

East Asian (EAS) AF: 0.115 AC: 598 AN: 5186

South Asian (SAS) AF: 0.145 AC: 699 AN: 4822

European-Finnish (FIN) AF: 0.133 AC: 1409 AN: 10606

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8724 AN: 68016

Other (OTH) AF: 0.156 AC: 329 AN: 2112

Alfa AF: 0.0625 Hom.: 85

Bravo AF: 0.155

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.49
PhyloP100		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11889731; hg19: chr2-31752857;