rs612224

Variant names:

• chr2-31586801-C-A
• rs612224
• XM_011533072.3:c.27-53035G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-31586801-C-A
• chr2-31586801-C-G
• chr2-31586801-C-T

Variant summary

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

The ENST00000817056.1(ENSG00000306342):​n.541-240G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,018 control chromosomes in the GnomAD database, including 40,943 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 0.73 (40943 hom., cov: 31)
• Consequence: ENSG00000306342 ENST00000817056.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546
• Publications: 3 publications found

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 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: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia

ENSG00000306342 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.826 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000306342	ENST00000817056.1		n.541-240G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110834 AN: 151900 Hom.: 40889 Cov.: 31

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.757

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.730 AC: 110949 AN: 152018 Hom.: 40943 Cov.: 31 AF XY: 0.727 AC XY: 54054 AN XY: 74308

African (AFR) AF: 0.833 AC: 34556 AN: 41486

American (AMR) AF: 0.693 AC: 10589 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.757 AC: 2628 AN: 3472

East Asian (EAS) AF: 0.547 AC: 2818 AN: 5156

South Asian (SAS) AF: 0.624 AC: 2995 AN: 4796

European-Finnish (FIN) AF: 0.718 AC: 7580 AN: 10552

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47368 AN: 67960

Other (OTH) AF: 0.728 AC: 1536 AN: 2110

Alfa AF: 0.705 Hom.: 46511

Bravo AF: 0.732

Asia WGS AF: 0.592 AC: 2058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.95
DANN	Benign	0.34
PhyloP100		-0.55

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs612224;

hg19: chr2-31811870;