rs61338903

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_000500.9(CYP21A2):c.29_31delTGC(p.Leu10del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,604 control chromosomes in the GnomAD database, including 6,037 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6037 hom., cov: 24)

Exomes 𝑓: 0.30 ( 66363 hom. )

Failed GnomAD Quality Control

Consequence

CYP21A2
NM_000500.9 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.46

Publications

8 publications found

Variant links:

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]

CYP21A2 Gene-Disease associations (from GenCC):

classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, salt wasting form
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency, simple virilizing form
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CYP21A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_000500.9

BP6

Variant 6-32038437-CCTG-C is Benign according to our data. Variant chr6-32038437-CCTG-C is described in ClinVar as Benign. ClinVar VariationId is 93160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CYP21A2	NM_000500.9 link	c.29_31delTGC	p.Leu10del	disruptive_inframe_deletion	Exon 1 of 10	ENST00000644719.2	NP_000491.4
CYP21A2	NM_001128590.4 link	c.29_31delTGC	p.Leu10del	disruptive_inframe_deletion	Exon 1 of 9		NP_001122062.3
CYP21A2	NM_001368143.2 link	c.-396_-394delTGC		5_prime_UTR_variant	Exon 1 of 10		NP_001355072.1
CYP21A2	NM_001368144.2 link	c.-306_-304delTGC		5_prime_UTR_variant	Exon 1 of 9		NP_001355073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP21A2	ENST00000644719.2 link	c.29_31delTGC	p.Leu10del	disruptive_inframe_deletion	Exon 1 of 10		NM_000500.9	ENSP00000496625.1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38005

AN:

151486

Hom.:

6030

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0653

Gnomad AMI

AF:

0.425

Gnomad AMR

AF:

0.368

Gnomad ASJ

AF:

0.462

Gnomad EAS

AF:

0.198

Gnomad SAS

AF:

0.239

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.340

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.250

GnomAD2 exomes

AF:

0.309

AC:

48291

AN:

156350

AF XY:

0.302

show subpopulations

Gnomad AFR exome

AF:

0.0530

Gnomad AMR exome

AF:

0.436

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.339

Gnomad NFE exome

AF:

0.309

Gnomad OTH exome

AF:

0.308

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.299

AC:

419054

AN:

1401396

Hom.:

66363

AF XY:

0.299

AC XY:

207021

AN XY:

691912

show subpopulations

African (AFR)

AF:

0.0611

AC:

1939

AN:

31726

American (AMR)

AF:

0.426

AC:

15514

AN:

36434

Ashkenazi Jewish (ASJ)

AF:

0.451

AC:

11360

AN:

25214

East Asian (EAS)

AF:

0.240

AC:

8755

AN:

36490

South Asian (SAS)

AF:

0.248

AC:

19830

AN:

80026

European-Finnish (FIN)

AF:

0.339

AC:

16374

AN:

48338

Middle Eastern (MID)

AF:

0.323

AC:

1637

AN:

5072

European-Non Finnish (NFE)

AF:

0.303

AC:

327094

AN:

1080050

Other (OTH)

AF:

0.285

AC:

16551

AN:

58046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

20225

40450

60674

80899

101124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10580

21160

31740

42320

52900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.251

AC:

38018

AN:

151604

Hom.:

6037

Cov.:

AF XY:

0.254

AC XY:

18835

AN XY:

74048

show subpopulations

African (AFR)

AF:

0.0651

AC:

2702

AN:

41478

American (AMR)

AF:

0.368

AC:

5613

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.462

AC:

1597

AN:

3454

East Asian (EAS)

AF:

0.199

AC:

1018

AN:

5126

South Asian (SAS)

AF:

0.239

AC:

1148

AN:

4800

European-Finnish (FIN)

AF:

0.349

AC:

3667

AN:

10496

Middle Eastern (MID)

AF:

0.348

AC:

101

AN:

290

European-Non Finnish (NFE)

AF:

0.314

AC:

21261

AN:

67712

Other (OTH)

AF:

0.251

AC:

526

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1202

2404

3606

4808

6010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.228

Hom.:

952

Bravo

AF:

0.247

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jan 21, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jul 18, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Mutation Taster

=72/28

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over