rs2300697

Variant names:

• chr2-31561567-C-T
• rs2300697
• NM_000348.4:c.281+19053G>A

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+19053G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 152,008 control chromosomes in the GnomAD database, including 28,900 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 0.61 (28900 hom., cov: 32)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• Publications: 10 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: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia

ENSG00000228563 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	NM_000348.4	MANE Select	c.281+19053G>A		intron	N/A	NP_000339.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	ENST00000622030.2	TSL:1 MANE Select	c.281+19053G>A		intron	N/A	ENSP00000477587.1	P31213
	SRD5A2	ENST00000882642.1		c.281+19053G>A		intron	N/A	ENSP00000552701.1
	SRD5A2	ENST00000882643.1		c.281+19053G>A		intron	N/A	ENSP00000552702.1

Frequencies

GnomAD3 genomes AF: 0.611 AC: 92787 AN: 151890 Hom.: 28852 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.560

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.611 AC: 92883 AN: 152008 Hom.: 28900 Cov.: 32 AF XY: 0.611 AC XY: 45390 AN XY: 74270

African (AFR) AF: 0.716 AC: 29701 AN: 41470

American (AMR) AF: 0.560 AC: 8562 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2347 AN: 3464

East Asian (EAS) AF: 0.464 AC: 2398 AN: 5172

South Asian (SAS) AF: 0.507 AC: 2439 AN: 4814

European-Finnish (FIN) AF: 0.625 AC: 6595 AN: 10548

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38889 AN: 67946

Other (OTH) AF: 0.590 AC: 1243 AN: 2108

Alfa AF: 0.585 Hom.: 81704

Bravo AF: 0.611

Asia WGS AF: 0.454 AC: 1582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.0
DANN	Benign	0.52
PhyloP100		-0.36

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: rs2300697; hg19: chr2-31786637;