rs138498156

chr6-32038437-C-CCTGchr6-32038437-CCTG-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP3 BP6

The NM_000500.9(CYP21A2):c.29_31dup(p.Leu10dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000050 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP21A2 NM_000500.9 inframe_insertion
• Clinical Significance: Benign no assertion criteria provided B:1 O:1
• Conservation: PhyloP100: 1.41

Genes affected

CYP21A2 (HGNC:2600): (cytochrome P450 family 21 subfamily A member 2) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for the synthesis of steroid hormones including cortisol and aldosterone. Mutations in this gene cause congenital adrenal hyperplasia. A related pseudogene is located near this gene; gene conversion events involving the functional gene and the pseudogene are thought to account for many cases of steroid 21-hydroxylase deficiency. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_000500.9
• BP6: Variant 6-32038437-C-CCTG is Benign according to our data. Variant chr6-32038437-C-CCTG is described in ClinVar as [Benign]. Clinvar id is 12162.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP21A2	NM_000500.9	c.29_31dup	p.Leu10dup	inframe_insertion	1/10	ENST00000644719.2
CYP21A2	NM_001128590.4	c.29_31dup	p.Leu10dup	inframe_insertion	1/9
CYP21A2	NM_001368143.2	c.-396_-394dup		5_prime_UTR_variant	1/10
CYP21A2	NM_001368144.2	c.-306_-304dup		5_prime_UTR_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP21A2	ENST00000644719.2	c.29_31dup	p.Leu10dup	inframe_insertion	1/10		NM_000500.9	P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD3 exomes AF: 0.0000128 AC: 2 AN: 156350 Hom.: 0 AF XY: 0.0000119 AC XY: 1 AN XY: 84000

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000851

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000499 AC: 7 AN: 1402506 Hom.: 0 Cov.: 3 AF XY: 0.00000578 AC XY: 4 AN XY: 692462

Gnomad4 AFR exome AF: 0.0000315

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000749

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

21-HYDROXYLASE POLYMORPHISM Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jun 01, 1987

- -

Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency Other:1

not provided, no classification provided

literature only

GeneReviews

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs61338903; hg19: chr6-32006214;