rs1042578

Variant names:

• chr2-31524644-C-T
• rs1042578
• NM_000348.4:c.*1552G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: 0.0400
• Publications: 7 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 -20 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 VariationId is 97419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000348.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	NM_000348.4	MANE Select	c.*1552G>A		3_prime_UTR	Exon 5 of 5	NP_000339.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	ENST00000622030.2	TSL:1 MANE Select	c.*1552G>A		3_prime_UTR	Exon 5 of 5	ENSP00000477587.1

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

African (AFR) AF: 0.249 AC: 927 AN: 3724

American (AMR) AF: 0.110 AC: 262 AN: 2388

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 1292 AN: 4944

East Asian (EAS) AF: 0.139 AC: 1527 AN: 10988

South Asian (SAS) AF: 0.142 AC: 97 AN: 684

European-Finnish (FIN) AF: 0.179 AC: 10 AN: 56

Middle Eastern (MID) AF: 0.241 AC: 115 AN: 478

European-Non Finnish (NFE) AF: 0.133 AC: 6393 AN: 48098

Other (OTH) AF: 0.155 AC: 1012 AN: 6542

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

African (AFR) AF: 0.247 AC: 10228 AN: 41488

American (AMR) AF: 0.110 AC: 1684 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 941 AN: 3468

East Asian (EAS) AF: 0.107 AC: 553 AN: 5188

South Asian (SAS) AF: 0.145 AC: 702 AN: 4828

European-Finnish (FIN) AF: 0.132 AC: 1396 AN: 10594

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8639 AN: 67990

Other (OTH) AF: 0.160 AC: 338 AN: 2114

Alfa AF: 0.142 Hom.: 3279

Bravo AF: 0.165

Asia WGS AF: 0.137 AC: 476 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency (1)
-	-	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.30
PhyloP100		0.040

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: rs1042578; hg19: chr2-31749714;