Variant 2-31525140-C-G 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.*1056G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0431 in 220,364 control chromosomes in the GnomAD database, including 354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 264 hom., cov: 32)

Exomes 𝑓: 0.042 ( 90 hom. )

Consequence

SRD5A2
NM_000348.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.59

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-31525140-C-G is Benign according to our data. Variant chr2-31525140-C-G is described in ClinVar as [Benign]. Clinvar id is 335807.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
SRD5A2	NM_000348.4 linkuse as main transcript	c.*1056G>C	3_prime_UTR_variant	5/5	ENST00000622030.2
SRD5A2	XM_011533069.3 linkuse as main transcript	c.*1056G>C	3_prime_UTR_variant	5/5
SRD5A2	XM_011533072.3 linkuse as main transcript	c.*1056G>C	3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A2	ENST00000622030.2 linkuse as main transcript	c.*1056G>C		3_prime_UTR_variant	5/5	1	NM_000348.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0438

AC:

6652

AN:

152042

Hom.:

260

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.0932

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.0369

Gnomad FIN

AF:

0.0181

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0533

Gnomad OTH

AF:

0.0426

GnomAD4 exome

AF:

0.0416

AC:

2840

AN:

68210

Hom.:

Cov.:

AF XY:

0.0409

AC XY:

1289

AN XY:

31550

show subpopulations

Gnomad4 AFR exome

AF:

0.00884

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.0241

Gnomad4 EAS exome

AF:

0.000297

Gnomad4 SAS exome

AF:

0.0554

Gnomad4 FIN exome

AF:

0.0556

Gnomad4 NFE exome

AF:

0.0510

Gnomad4 OTH exome

AF:

0.0479

GnomAD4 genome

AF:

0.0438

AC:

6665

AN:

152154

Hom.:

264

Cov.:

AF XY:

0.0434

AC XY:

3230

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.00289

Gnomad4 SAS

AF:

0.0376

Gnomad4 FIN

AF:

0.0181

Gnomad4 NFE

AF:

0.0533

Gnomad4 OTH

AF:

0.0436

Alfa

AF:

0.0470

Hom.:

112

Bravo

AF:

0.0494

Asia WGS

AF:

0.0340

AC:

120

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.23

DANN

Benign

0.39

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

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