2-31568349-G-A

Variant names:

• chr2-31568349-G-A
• rs11675297
• NM_000348.4:c.281+12271C>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.281+12271C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,118 control chromosomes in the GnomAD database, including 1,789 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 0.11 (1789 hom., cov: 32)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A2	NM_000348.4	c.281+12271C>T		intron_variant	Intron 1 of 4	ENST00000622030.2	NP_000339.2
SRD5A2	XM_011533072.3	c.27-34583C>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.281+12271C>T		intron_variant	Intron 1 of 4	1	NM_000348.4	ENSP00000477587.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17227 AN: 152000 Hom.: 1770 Cov.: 32

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.0738

Gnomad SAS AF: 0.0535

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0437

Gnomad OTH AF: 0.0920

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

GnomAD4 genome AF: 0.114 AC: 17296 AN: 152118 Hom.: 1789 Cov.: 32 AF XY: 0.110 AC XY: 8179 AN XY: 74366

African (AFR) AF: 0.273 AC: 11339 AN: 41480

American (AMR) AF: 0.0920 AC: 1407 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 66 AN: 3472

East Asian (EAS) AF: 0.0740 AC: 380 AN: 5138

South Asian (SAS) AF: 0.0532 AC: 256 AN: 4816

European-Finnish (FIN) AF: 0.0584 AC: 619 AN: 10592

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0437 AC: 2974 AN: 68016

Other (OTH) AF: 0.0929 AC: 196 AN: 2110

Alfa AF: 0.0928 Hom.: 157

Bravo AF: 0.124

Asia WGS AF: 0.117 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.4
DANN	Benign	0.37
PhyloP100		-0.54

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

Other links and lift over

dbSNP: rs11675297; hg19: chr2-31793419;