Variant chr2-31524923-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000348.4(SRD5A2):c.*1273A>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 0.00962 in 224,642 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0096 ( 22 hom., cov: 32)

Exomes 𝑓: 0.0096 ( 3 hom. )

Consequence

SRD5A2
NM_000348.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.523

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 (BayesDel_noAF=-0.81).

BP6

Variant 2-31524923-T-C is Benign according to our data. Variant chr2-31524923-T-C is described in ClinVar as [Benign]. Clinvar id is 335803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00965 (1469/152302) while in subpopulation SAS AF= 0.0444 (214/4824). AF 95% confidence interval is 0.0395. There are 22 homozygotes in gnomad4. There are 733 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
SRD5A2	NM_000348.4 linkuse as main transcript	c.*1273A>G	3_prime_UTR_variant	5/5	ENST00000622030.2
SRD5A2	XM_011533069.3 linkuse as main transcript	c.*1273A>G	3_prime_UTR_variant	5/5
SRD5A2	XM_011533072.3 linkuse as main transcript	c.*1273A>G	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.*1273A>G		3_prime_UTR_variant	5/5	1	NM_000348.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00967

AC:

1472

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.0418

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.000576

Gnomad SAS

AF:

0.0449

Gnomad FIN

AF:

0.0155

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.0110

GnomAD4 exome

AF:

0.00958

AC:

693

AN:

72340

Hom.:

Cov.:

AF XY:

0.00943

AC XY:

314

AN XY:

33312

show subpopulations

Gnomad4 AFR exome

AF:

0.00263

Gnomad4 AMR exome

AF:

0.00503

Gnomad4 ASJ exome

AF:

0.00725

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0492

Gnomad4 FIN exome

AF:

0.0179

Gnomad4 NFE exome

AF:

0.0123

Gnomad4 OTH exome

AF:

0.00874

GnomAD4 genome

AF:

0.00965

AC:

1469

AN:

152302

Hom.:

Cov.:

AF XY:

0.00984

AC XY:

733

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.00517

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0444

Gnomad4 FIN

AF:

0.0155

Gnomad4 NFE

AF:

0.0125

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.00714

Asia WGS

AF:

0.0270

AC:

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

-0.81

CADD

Benign

5.5

DANN

Benign

0.59

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