NM_000348.4:c.282-6720G>T

Variant names:

• chr2-31540486-C-A
• rs4952220
• NM_000348.4:c.282-6720G>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.282-6720G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,768 control chromosomes in the GnomAD database, including 20,883 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 0.52 (20883 hom., cov: 32)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.474
• Publications: 9 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SRD5A2	NM_000348.4	c.282-6720G>T		intron_variant	Intron 1 of 4	ENST00000622030.2	NP_000339.2
SRD5A2	XM_011533069.3	c.60-6720G>T		intron_variant	Intron 1 of 4		XP_011531371.1
SRD5A2	XM_011533072.3	c.27-6720G>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.282-6720G>T		intron_variant	Intron 1 of 4	1	NM_000348.4	ENSP00000477587.1
ENSG00000228563	ENST00000435713.1	n.255+12786C>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.521 AC: 78963 AN: 151650 Hom.: 20886 Cov.: 32

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.520 AC: 78986 AN: 151768 Hom.: 20883 Cov.: 32 AF XY: 0.523 AC XY: 38776 AN XY: 74166

African (AFR) AF: 0.433 AC: 17893 AN: 41336

American (AMR) AF: 0.551 AC: 8408 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1680 AN: 3468

East Asian (EAS) AF: 0.368 AC: 1901 AN: 5162

South Asian (SAS) AF: 0.478 AC: 2302 AN: 4812

European-Finnish (FIN) AF: 0.586 AC: 6173 AN: 10532

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.571 AC: 38779 AN: 67878

Other (OTH) AF: 0.530 AC: 1116 AN: 2106

Alfa AF: 0.550 Hom.: 34828

Bravo AF: 0.513

Asia WGS AF: 0.384 AC: 1336 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	0.60
DANN	Benign	0.16
PhyloP100		-0.47

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: rs4952220; hg19: chr2-31765556;