chr2-31531447-CATT-C

Position:

• chr2-31531447-CATT-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1 PM2 PM4_Supporting PP5

The NM_000348.4(SRD5A2):​c.468_470del​(p.Met157del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SRD5A2 NM_000348.4 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.84

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]

(HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM1: In a helix (size 24) in uniprot entity S5A2_HUMAN there are 5 pathogenic changes around while only 1 benign (83%) in NM_000348.4
• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_000348.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 2-31531447-CATT-C is Pathogenic according to our data. Variant chr2-31531447-CATT-C is described in ClinVar as [Pathogenic]. Clinvar id is 3338.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SRD5A2	NM_000348.4	c.468_470del	p.Met157del	inframe_deletion	3/5	ENST00000622030.2
SRD5A2	XM_011533069.3	c.246_248del	p.Met83del	inframe_deletion	3/5
SRD5A2	XM_011533072.3	c.213_215del	p.Met72del	inframe_deletion	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SRD5A2	ENST00000622030.2	c.468_470del	p.Met157del	inframe_deletion	3/5	1	NM_000348.4	P1
	ENST00000435713.1	n.255+3748_255+3750del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 1995

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs587776566; hg19: chr2-31756517;