NM_000348.4:c.281+1751A>C

Variant names:

• chr2-31578869-T-G
• rs765138
• NM_000348.4:c.281+1751A>C

Variant summary

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

The NM_000348.4(SRD5A2):​c.281+1751A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 151,986 control chromosomes in the GnomAD database, including 30,044 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 0.63 (30044 hom., cov: 33)
• Consequence: SRD5A2 NM_000348.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.231
• Publications: 6 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000348.4. 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
	SRD5A2	NM_000348.4	MANE Select	c.281+1751A>C		intron	N/A	NP_000339.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	ENST00000622030.2	TSL:1 MANE Select	c.281+1751A>C		intron	N/A	ENSP00000477587.1	P31213
	SRD5A2	ENST00000882642.1		c.281+1751A>C		intron	N/A	ENSP00000552701.1
	SRD5A2	ENST00000882643.1		c.281+1751A>C		intron	N/A	ENSP00000552702.1

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95106 AN: 151868 Hom.: 30001 Cov.: 33

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.618

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

GnomAD4 genome AF: 0.626 AC: 95196 AN: 151986 Hom.: 30044 Cov.: 33 AF XY: 0.626 AC XY: 46514 AN XY: 74288

African (AFR) AF: 0.688 AC: 28508 AN: 41452

American (AMR) AF: 0.600 AC: 9159 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2397 AN: 3472

East Asian (EAS) AF: 0.486 AC: 2510 AN: 5160

South Asian (SAS) AF: 0.529 AC: 2552 AN: 4820

European-Finnish (FIN) AF: 0.641 AC: 6756 AN: 10540

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.608 AC: 41306 AN: 67954

Other (OTH) AF: 0.612 AC: 1292 AN: 2110

Alfa AF: 0.631 Hom.: 3942

Bravo AF: 0.626

Asia WGS AF: 0.477 AC: 1658 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.4
DANN	Benign	0.53
PhyloP100		0.23

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

Other links and lift over

dbSNP: rs765138; hg19: chr2-31803939;