2-31580962-C-G

Position:

• chr2-31580962-C-G

Variant summary

Our verdict is Benign. Variant got -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:3 O:1
• Conservation: PhyloP100: 0.989

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 97386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-31580962-C-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A2	XM_011533072.3	c.27-47196G>C		intron_variant
SRD5A2	NM_000348.4			upstream_gene_variant		ENST00000622030.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A2	ENST00000622030.2			upstream_gene_variant		1	NM_000348.4	P1

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

Gnomad4 AFR exome AF: 0.708

Gnomad4 AMR exome AF: 0.629

Gnomad4 ASJ exome AF: 0.767

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.628

Gnomad4 FIN exome AF: 0.677

Gnomad4 NFE exome AF: 0.695

Gnomad4 OTH exome AF: 0.690

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

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.668

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.691

Alfa AF: 0.678 Hom.: 17553

Bravo AF: 0.682

Asia WGS AF: 0.514 AC: 1789 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not provided Benign:1 Other:1

not provided, no classification provided	literature only	University of Sydney Medical Foundation	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	16
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

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