rs1057519068

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4

The NM_000500.9(CYP21A2):​c.830_841delTCCTGGAAGGGC​(p.Leu277_Gly280del) variant causes a disruptive inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as no classification for the single variant (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

CYP21A2
NM_000500.9 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.59
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000500.9.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYP21A2NM_000500.9 linkuse as main transcriptc.830_841delTCCTGGAAGGGC p.Leu277_Gly280del disruptive_inframe_deletion 7/10 ENST00000644719.2 NP_000491.4 P08686Q16874Q08AG9
CYP21A2NM_001128590.4 linkuse as main transcriptc.740_751delTCCTGGAAGGGC p.Leu247_Gly250del disruptive_inframe_deletion 6/9 NP_001122062.3 P08686Q08AG9
CYP21A2NM_001368143.2 linkuse as main transcriptc.425_436delTCCTGGAAGGGC p.Leu142_Gly145del disruptive_inframe_deletion 7/10 NP_001355072.1
CYP21A2NM_001368144.2 linkuse as main transcriptc.425_436delTCCTGGAAGGGC p.Leu142_Gly145del disruptive_inframe_deletion 6/9 NP_001355073.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYP21A2ENST00000644719.2 linkuse as main transcriptc.830_841delTCCTGGAAGGGC p.Leu277_Gly280del disruptive_inframe_deletion 7/10 NM_000500.9 ENSP00000496625.1 Q16874

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1057519068; hg19: chr6-32007870; API