2-31612299-G-A

Variant names:

• chr2-31612299-G-A
• rs508562
• ENST00000817056.1:n.541-25738C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000817056.1(ENSG00000306342):​n.541-25738C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 148,764 control chromosomes in the GnomAD database, including 25,532 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 0.59 (25532 hom., cov: 28)
• Consequence: ENSG00000306342 ENST00000817056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 1 publications found

Genes affected

ENSG00000306342 (HGNC:):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000817056.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000306342	ENST00000817056.1		n.541-25738C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.587 AC: 87342 AN: 148692 Hom.: 25514 Cov.: 28

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.542

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.582

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.588 AC: 87399 AN: 148764 Hom.: 25532 Cov.: 28 AF XY: 0.587 AC XY: 42601 AN XY: 72570

African (AFR) AF: 0.640 AC: 25805 AN: 40318

American (AMR) AF: 0.608 AC: 9109 AN: 14970

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1711 AN: 3454

East Asian (EAS) AF: 0.446 AC: 2266 AN: 5084

South Asian (SAS) AF: 0.520 AC: 2476 AN: 4762

European-Finnish (FIN) AF: 0.598 AC: 5792 AN: 9690

Middle Eastern (MID) AF: 0.552 AC: 160 AN: 290

European-Non Finnish (NFE) AF: 0.571 AC: 38366 AN: 67228

Other (OTH) AF: 0.580 AC: 1200 AN: 2068

Alfa AF: 0.436 Hom.: 1134

Bravo AF: 0.587

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.085
DANN	Benign	0.51
PhyloP100		-1.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs508562; hg19: chr2-31837368;