Genetic Variant SRD5A2:c.*2238A>G (chr2-31523958-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000348.4(SRD5A2):c.*2238A>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 217,676 control chromosomes in the GnomAD database, including 2,167 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.13 ( 1504 hom., cov: 32)

Exomes 𝑓: 0.13 ( 663 hom. )

Consequence

SRD5A2
NM_000348.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.804

Publications

3 publications found

Variant links:

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

SRD5A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	NM_000348.4	MANE Select	c.*2238A>G		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.*2238A>G		3_prime_UTR	Exon 5 of 5	ENSP00000477587.1

Frequencies

GnomAD3 genomes

AF:

0.133

AC:

20244

AN:

152090

Hom.:

1494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.0877

Gnomad AMR

AF:

0.0953

Gnomad ASJ

AF:

0.268

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.0982

Gnomad FIN

AF:

0.0990

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.104

Gnomad OTH

AF:

0.132

GnomAD4 exome

AF:

0.129

AC:

8467

AN:

65466

Hom.:

663

Cov.:

AF XY:

0.131

AC XY:

3976

AN XY:

30390

show subpopulations

African (AFR)

AF:

0.210

AC:

629

AN:

3000

American (AMR)

AF:

0.0983

AC:

191

AN:

1944

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

1065

AN:

4138

East Asian (EAS)

AF:

0.139

AC:

1322

AN:

9544

South Asian (SAS)

AF:

0.0915

AC:

AN:

568

European-Finnish (FIN)

AF:

0.130

AC:

AN:

Middle Eastern (MID)

AF:

0.193

AC:

AN:

398

European-Non Finnish (NFE)

AF:

0.109

AC:

4400

AN:

40354

Other (OTH)

AF:

0.132

AC:

725

AN:

5474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

368

737

1105

1474

1842

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.133

AC:

20287

AN:

152210

Hom.:

1504

Cov.:

AF XY:

0.132

AC XY:

9799

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.201

AC:

8334

AN:

41510

American (AMR)

AF:

0.0953

AC:

1457

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

932

AN:

3472

East Asian (EAS)

AF:

0.105

AC:

541

AN:

5170

South Asian (SAS)

AF:

0.0989

AC:

477

AN:

4822

European-Finnish (FIN)

AF:

0.0990

AC:

1051

AN:

10612

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.104

AC:

7081

AN:

68020

Other (OTH)

AF:

0.132

AC:

278

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

888

1777

2665

3554

4442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

204

408

612

816

1020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.117

Hom.:

537

Bravo

AF:

0.138

Asia WGS

AF:

0.106

AC:

367

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.2

(source)

DANN

Benign

0.44

PhyloP100

-0.80

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over