chr2-31525347-T-C

Variant names:

• chr2-31525347-T-C
• rs9332975
• NM_000348.4:c.*849A>G

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.*849A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 226,138 control chromosomes in the GnomAD database, including 2,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1502 hom., cov: 32)
  • Exomes 𝑓: 0.13 (746 hom.)
• Consequence: SRD5A2 NM_000348.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -0.882
• Publications: 15 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 2-31525347-T-C is Benign according to our data. Variant chr2-31525347-T-C is described in ClinVar as Benign. ClinVar VariationId is 97417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	NM_000348.4	MANE Select	c.*849A>G		3_prime_UTR	Exon 5 of 5	NP_000339.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	ENST00000622030.2	TSL:1 MANE Select	c.*849A>G		3_prime_UTR	Exon 5 of 5	ENSP00000477587.1	P31213
	SRD5A2	ENST00000882642.1		c.*849A>G		3_prime_UTR	Exon 6 of 6	ENSP00000552701.1
	SRD5A2	ENST00000882643.1		c.*849A>G		3_prime_UTR	Exon 4 of 4	ENSP00000552702.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20246 AN: 152096 Hom.: 1492 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.0945

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0983

Gnomad FIN AF: 0.0986

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.129 AC: 9557 AN: 73924 Hom.: 746 Cov.: 0 AF XY: 0.130 AC XY: 4438 AN XY: 34108

African (AFR) AF: 0.212 AC: 738 AN: 3480

American (AMR) AF: 0.0929 AC: 208 AN: 2238

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 1207 AN: 4690

East Asian (EAS) AF: 0.139 AC: 1471 AN: 10576

South Asian (SAS) AF: 0.0905 AC: 59 AN: 652

European-Finnish (FIN) AF: 0.148 AC: 8 AN: 54

Middle Eastern (MID) AF: 0.213 AC: 97 AN: 456

European-Non Finnish (NFE) AF: 0.109 AC: 4969 AN: 45588

Other (OTH) AF: 0.129 AC: 800 AN: 6190

GnomAD4 genome AF: 0.133 AC: 20289 AN: 152214 Hom.: 1502 Cov.: 32 AF XY: 0.132 AC XY: 9793 AN XY: 74426

African (AFR) AF: 0.201 AC: 8338 AN: 41522

American (AMR) AF: 0.0945 AC: 1446 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 933 AN: 3470

East Asian (EAS) AF: 0.106 AC: 549 AN: 5174

South Asian (SAS) AF: 0.0990 AC: 478 AN: 4830

European-Finnish (FIN) AF: 0.0986 AC: 1046 AN: 10606

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7082 AN: 68000

Other (OTH) AF: 0.132 AC: 279 AN: 2112

Alfa AF: 0.121 Hom.: 3813

Bravo AF: 0.138

Asia WGS AF: 0.105 AC: 366 AN: 3476

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	-0.93
CADD	Benign	0.55
DANN	Benign	0.76
PhyloP100		-0.88

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: rs9332975; hg19: chr2-31750417;