rs2300700

Variant names:

• chr2-31561922-G-A
• rs2300700
• NM_000348.4:c.281+18698C>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+18698C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 151,964 control chromosomes in the GnomAD database, including 13,726 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 0.42 (13726 hom., cov: 33)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A2	NM_000348.4	c.281+18698C>T		intron_variant	Intron 1 of 4	ENST00000622030.2	NP_000339.2
SRD5A2	XM_011533072.3	c.27-28156C>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+18698C>T		intron_variant	Intron 1 of 4	1	NM_000348.4	ENSP00000477587.1
ENSG00000228563	ENST00000435713.1	n.256-1152G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.421 AC: 63890 AN: 151844 Hom.: 13726 Cov.: 33

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.421 AC: 63918 AN: 151964 Hom.: 13726 Cov.: 33 AF XY: 0.423 AC XY: 31395 AN XY: 74270

African (AFR) AF: 0.342 AC: 14179 AN: 41450

American (AMR) AF: 0.440 AC: 6710 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1394 AN: 3470

East Asian (EAS) AF: 0.357 AC: 1846 AN: 5174

South Asian (SAS) AF: 0.403 AC: 1939 AN: 4814

European-Finnish (FIN) AF: 0.507 AC: 5341 AN: 10532

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.458 AC: 31091 AN: 67948

Other (OTH) AF: 0.406 AC: 856 AN: 2110

Alfa AF: 0.447 Hom.: 7154

Bravo AF: 0.412

Asia WGS AF: 0.338 AC: 1176 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.0
DANN	Benign	0.36
PhyloP100		-0.74

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: rs2300700; hg19: chr2-31786992;