2-31580962-C-G

Variant names:

• chr2-31580962-C-G
• rs632148
• XM_011533072.3:c.27-47196G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The XM_011533072.3(SRD5A2):​c.27-47196G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 1,528,114 control chromosomes in the GnomAD database, including 359,944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.69 (35945 hom., cov: 35)
  • Exomes 𝑓: 0.69 (323999 hom.)
• Consequence: SRD5A2 XM_011533072.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: 0.989
• Publications: 18 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 2-31580962-C-G is Benign according to our data. Variant chr2-31580962-C-G is described in ClinVar as Benign. ClinVar VariationId is 97386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000622030.2. 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.-62G>C		upstream_gene	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.-62G>C		upstream_gene	N/A	ENSP00000477587.1	P31213
	SRD5A2	ENST00000882642.1		c.-62G>C		upstream_gene	N/A	ENSP00000552701.1
	SRD5A2	ENST00000882643.1		c.-62G>C		upstream_gene	N/A	ENSP00000552702.1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104225 AN: 152092 Hom.: 35929 Cov.: 35

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.693

GnomAD4 exome AF: 0.685 AC: 942801 AN: 1375902 Hom.: 323999 Cov.: 27 AF XY: 0.683 AC XY: 462124 AN XY: 676188

African (AFR) AF: 0.708 AC: 22167 AN: 31326

American (AMR) AF: 0.629 AC: 24152 AN: 38422

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 17384 AN: 22676

East Asian (EAS) AF: 0.514 AC: 19355 AN: 37672

South Asian (SAS) AF: 0.628 AC: 48025 AN: 76422

European-Finnish (FIN) AF: 0.677 AC: 25614 AN: 37822

Middle Eastern (MID) AF: 0.725 AC: 2989 AN: 4122

European-Non Finnish (NFE) AF: 0.695 AC: 743753 AN: 1070414

Other (OTH) AF: 0.690 AC: 39362 AN: 57026

GnomAD4 genome AF: 0.685 AC: 104287 AN: 152212 Hom.: 35945 Cov.: 35 AF XY: 0.684 AC XY: 50921 AN XY: 74398

African (AFR) AF: 0.701 AC: 29139 AN: 41558

American (AMR) AF: 0.668 AC: 10218 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2655 AN: 3470

East Asian (EAS) AF: 0.473 AC: 2430 AN: 5140

South Asian (SAS) AF: 0.616 AC: 2970 AN: 4822

European-Finnish (FIN) AF: 0.692 AC: 7348 AN: 10612

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47196 AN: 67994

Other (OTH) AF: 0.691 AC: 1458 AN: 2110

Alfa AF: 0.678 Hom.: 17553

Bravo AF: 0.682

Asia WGS AF: 0.514 AC: 1789 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency (2)
-	-	2	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.50
PhyloP100		0.99
PromoterAI		0.045	Neutral

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: rs632148; hg19: chr2-31806031; COSMIC: COSV51870275;