rs74702388

Variant names:

• chr2-31525043-TAAA-T
• rs74702388
• NM_000348.4:c.*1150_*1152delTTT

Your query was ambiguous. Multiple possible variants found:

• chr2-31525043-TAAA-T
• chr2-31525043-TAAA-TA
• chr2-31525043-TAAA-TAA
• chr2-31525043-TAAA-TAAAA
• chr2-31525043-TAAA-TAAAAA
• chr2-31525043-TAAA-TAAAAAA
• chr2-31525043-TAAA-TAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000348.4(SRD5A2):​c.*1150_*1152delTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 50,446 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: SRD5A2 NM_000348.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.414
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.*1150_*1152delTTT		3_prime_UTR	Exon 5 of 5	NP_000339.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SRD5A2	ENST00000622030.2	TSL:1 MANE Select	c.*1150_*1152delTTT		3_prime_UTR	Exon 5 of 5	ENSP00000477587.1	P31213
	SRD5A2	ENST00000882642.1		c.*1150_*1152delTTT		3_prime_UTR	Exon 6 of 6	ENSP00000552701.1
	SRD5A2	ENST00000882643.1		c.*1150_*1152delTTT		3_prime_UTR	Exon 4 of 4	ENSP00000552702.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000198 AC: 1 AN: 50446 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 23402

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 2226

American (AMR) AF: 0.00 AC: 0 AN: 1448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3214

East Asian (EAS) AF: 0.000127 AC: 1 AN: 7886

South Asian (SAS) AF: 0.00 AC: 0 AN: 418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 324

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 30674

Other (OTH) AF: 0.00 AC: 0 AN: 4216

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.41

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: rs74702388; hg19: chr2-31750113;