Variant 2-31580636-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000348.4(SRD5A2):c.265C>G(p.Leu89Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 1,576,058 control chromosomes in the GnomAD database, including 383,689 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 38041 hom., cov: 37)

Exomes 𝑓: 0.70 ( 345648 hom. )

Consequence

SRD5A2
NM_000348.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 0.123

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2003112E-6).

BP6

Variant 2-31580636-G-C is Benign according to our data. Variant chr2-31580636-G-C is described in ClinVar as [Benign]. Clinvar id is 97400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SRD5A2	NM_000348.4 linkuse as main transcript	c.265C>G	p.Leu89Val	missense_variant	1/5	ENST00000622030.2	NP_000339.2	P31213
SRD5A2	XM_011533072.3 linkuse as main transcript	c.27-46870C>G		intron_variant			XP_011531374.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SRD5A2	ENST00000622030.2 linkuse as main transcript	c.265C>G	p.Leu89Val	missense_variant	1/5	1	NM_000348.4	ENSP00000477587.1		P31213

Frequencies

GnomAD3 genomes

AF:

0.704

AC:

107162

AN:

152146

Hom.:

38009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.734

Gnomad AMR

AF:

0.676

Gnomad ASJ

AF:

0.756

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.607

Gnomad FIN

AF:

0.708

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.707

Gnomad OTH

AF:

0.710

GnomAD3 exomes

AF:

0.659

AC:

133781

AN:

202928

Hom.:

44741

AF XY:

0.660

AC XY:

72992

AN XY:

110600

show subpopulations

Gnomad AFR exome

AF:

0.746

Gnomad AMR exome

AF:

0.616

Gnomad ASJ exome

AF:

0.759

Gnomad EAS exome

AF:

0.446

Gnomad SAS exome

AF:

0.612

Gnomad FIN exome

AF:

0.697

Gnomad NFE exome

AF:

0.697

Gnomad OTH exome

AF:

0.689

GnomAD4 exome

AF:

0.695

AC:

989679

AN:

1423794

Hom.:

345648

Cov.:

AF XY:

0.692

AC XY:

488786

AN XY:

706000

show subpopulations

Gnomad4 AFR exome

AF:

0.750

Gnomad4 AMR exome

AF:

0.625

Gnomad4 ASJ exome

AF:

0.761

Gnomad4 EAS exome

AF:

0.505

Gnomad4 SAS exome

AF:

0.620

Gnomad4 FIN exome

AF:

0.694

Gnomad4 NFE exome

AF:

0.707

Gnomad4 OTH exome

AF:

0.699

GnomAD4 genome

AF:

0.704

AC:

107245

AN:

152264

Hom.:

38041

Cov.:

AF XY:

0.702

AC XY:

52301

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.745

Gnomad4 AMR

AF:

0.675

Gnomad4 ASJ

AF:

0.756

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.607

Gnomad4 FIN

AF:

0.708

Gnomad4 NFE

AF:

0.707

Gnomad4 OTH

AF:

0.707

Alfa

AF:

0.710

Hom.:

6825

Bravo

AF:

0.703

TwinsUK

AF:

0.707

AC:

2623

ALSPAC

AF:

0.702

AC:

2705

ESP6500AA

AF:

0.755

AC:

2946

ESP6500EA

AF:

0.710

AC:

5907

ExAC

AF:

0.637

AC:

75343

Asia WGS

AF:

0.508

AC:

1771

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

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

3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

4.0

DANN

Benign

0.73

FATHMM_MKL

Benign

0.015

MetaRNN

Benign

0.0000022

PrimateAI

Benign

0.38

Sift4G

Benign

0.66

Vest4

0.14

GERP RS

2.2

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over