chr2-31524644-C-T

Position:

• chr2-31524644-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000348.4(SRD5A2):​c.*1552G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 230,052 control chromosomes in the GnomAD database, including 3,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2223 hom., cov: 32)
  • Exomes 𝑓: 0.15 (1013 hom.)
• Consequence: SRD5A2 NM_000348.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 0.0400

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-31524644-C-T is Benign according to our data. Variant chr2-31524644-C-T is described in ClinVar as [Benign]. Clinvar id is 97419.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A2	NM_000348.4	c.*1552G>A		3_prime_UTR_variant	5/5	ENST00000622030.2
SRD5A2	XM_011533069.3	c.*1552G>A		3_prime_UTR_variant	5/5
SRD5A2	XM_011533072.3	c.*1552G>A		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A2	ENST00000622030.2	c.*1552G>A		3_prime_UTR_variant	5/5	1	NM_000348.4	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24601 AN: 152032 Hom.: 2204 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.149 AC: 11635 AN: 77902 Hom.: 1013 Cov.: 0 AF XY: 0.150 AC XY: 5384 AN XY: 35850

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.261

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.133

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.162 AC: 24663 AN: 152150 Hom.: 2223 Cov.: 32 AF XY: 0.160 AC XY: 11889 AN XY: 74378

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.160

Alfa AF: 0.140 Hom.: 2410

Bravo AF: 0.165

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency Benign:1

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. -

not provided Other:1

not provided, no classification provided

literature only

University of Sydney Medical Foundation

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.30

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: rs1042578; hg19: chr2-31749714;