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rs28383064

chr2-31529411-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000348.4(SRD5A2):c.594C>T(p.Ile198=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,613,936 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0034 ( 22 hom. )

Consequence

SRD5A2
NM_000348.4 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.463
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-31529411-G-A is Benign according to our data. Variant chr2-31529411-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 459639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-31529411-G-A is described in Lovd as [Benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.463 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SRD5A2NM_000348.4 linkuse as main transcriptc.594C>T p.Ile198= synonymous_variant 4/5 ENST00000622030.2
SRD5A2XM_011533069.3 linkuse as main transcriptc.372C>T p.Ile124= synonymous_variant 4/5
SRD5A2XM_011533072.3 linkuse as main transcriptc.339C>T p.Ile113= synonymous_variant 6/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SRD5A2ENST00000622030.2 linkuse as main transcriptc.594C>T p.Ile198= synonymous_variant 4/51 NM_000348.4 P1
ENST00000435713.1 linkuse as main transcriptn.255+1711G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00271
AC:
413
AN:
152230
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000699
Gnomad AMI
AF:
0.0132
Gnomad AMR
AF:
0.00484
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00226
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00379
Gnomad OTH
AF:
0.00718
GnomAD3 exomes
AF:
0.00283
AC:
704
AN:
248836
Hom.:
4
AF XY:
0.00279
AC XY:
377
AN XY:
135000
show subpopulations
Gnomad AFR exome
AF:
0.000452
Gnomad AMR exome
AF:
0.00264
Gnomad ASJ exome
AF:
0.0000995
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00105
Gnomad FIN exome
AF:
0.00265
Gnomad NFE exome
AF:
0.00435
Gnomad OTH exome
AF:
0.00430
GnomAD4 exome
AF:
0.00344
AC:
5027
AN:
1461590
Hom.:
22
Cov.:
31
AF XY:
0.00333
AC XY:
2418
AN XY:
727066
show subpopulations
Gnomad4 AFR exome
AF:
0.000538
Gnomad4 AMR exome
AF:
0.00259
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000788
Gnomad4 FIN exome
AF:
0.00311
Gnomad4 NFE exome
AF:
0.00401
Gnomad4 OTH exome
AF:
0.00280
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00271
AC:
413
AN:
152346
Hom.:
0
Cov.:
32
AF XY:
0.00270
AC XY:
201
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.000697
Gnomad4 AMR
AF:
0.00484
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00226
Gnomad4 NFE
AF:
0.00379
Gnomad4 OTH
AF:
0.00710
Alfa
AF:
0.00400
Hom.:
1
Bravo
AF:
0.00306
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022SRD5A2: BP4, BP7 -
Benign, criteria provided, single submitterclinical testingGeneDxAug 25, 2015- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoDec 07, 2017- -
3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
Cadd
Benign
6.7
Dann
Benign
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
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.

Other links and lift over

dbSNP: rs28383064; hg19: chr2-31754481; API