2-31578425-T-C

Variant names:

• chr2-31578425-T-C
• rs2268799
• NM_000348.4:c.281+2195A>G

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+2195A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,002 control chromosomes in the GnomAD database, including 31,265 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 0.64 (31265 hom., cov: 32)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A2	NM_000348.4	c.281+2195A>G		intron_variant	Intron 1 of 4	ENST00000622030.2	NP_000339.2
SRD5A2	XM_011533072.3	c.27-44659A>G		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+2195A>G		intron_variant	Intron 1 of 4	1	NM_000348.4	ENSP00000477587.1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96897 AN: 151884 Hom.: 31259 Cov.: 32

Gnomad AFR AF: 0.565

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.755

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.638 AC: 96942 AN: 152002 Hom.: 31265 Cov.: 32 AF XY: 0.639 AC XY: 47489 AN XY: 74308

African (AFR) AF: 0.565 AC: 23402 AN: 41422

American (AMR) AF: 0.648 AC: 9895 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2618 AN: 3468

East Asian (EAS) AF: 0.487 AC: 2519 AN: 5170

South Asian (SAS) AF: 0.573 AC: 2761 AN: 4818

European-Finnish (FIN) AF: 0.674 AC: 7120 AN: 10566

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46396 AN: 67966

Other (OTH) AF: 0.661 AC: 1395 AN: 2110

Alfa AF: 0.671 Hom.: 9389

Bravo AF: 0.631

Asia WGS AF: 0.487 AC: 1697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.7
DANN	Benign	0.41
PhyloP100		0.073

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2268799; hg19: chr2-31803495;