VCV002681112.2 - ClinVar

NM_000102.4(CYP17A1):c.973AAG[2] (p.Lys327del)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(2)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic/Likely pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000102.4(CYP17A1):c.973AAG[2] (p.Lys327del)

Variation ID: 2681112 Accession: VCV002681112.2

Type and length

Microsatellite, 3 bp

Location

Cytogenetic: 10q24.32 10: 102832669-102832671 (GRCh38) [ NCBI UCSC ] 10: 104592426-104592428 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 30, 2023	Aug 11, 2024	May 10, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000102.4:c.973AAG[2] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000093.1:p.Lys327del
NM_000102.4:c.979_981del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_000102.4:c.979_981delAAG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NC_000010.11:g.102832670TTC[2]
NC_000010.10:g.104592427TTC[2]
NG_007955.1:g.9857AAG[2]

... more HGVS ... less HGVS

Protein change

K327del

Other names

Canonical SPDI

NC_000010.11:102832668:CTTCTTCTTC:CTTCTTC

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CYP17A1		-	-	GRCh38 GRCh37	424	554

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Deficiency of steroid 17-alpha-monooxygenase	Pathogenic (1)	criteria provided, single submitter	Feb 20, 2023	RCV003468647.1
Congenital adrenal hyperplasia	Likely pathogenic (1)	criteria provided, single submitter	May 10, 2024	RCV004690416.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Feb 20, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Deficiency of steroid 17-alpha-monooxygenase Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004215429.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023
Likely pathogenic (May 10, 2024)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Congenital adrenal hyperplasia Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV005184943.1 First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024	Publications: PubMed (3) PubMed: 17192295‚ 33864926‚ 22954317 Comment: Variant summary: CYP17A1 c.979_981delAAG (p.Lys327del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele … (more) Variant summary: CYP17A1 c.979_981delAAG (p.Lys327del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 4e-06 in 251444 control chromosomes. c.979_981delAAG has been reported in the literature as homozygous or compound heterozygous with another pathogenic variant in individuals affected with Congenital Adrenal Hyperplasia (Rosa_2007, Yao_2013). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% production of 17-OH progesterone (17OHP) as a measure of 17alpha-hydroxylase activity compared to wild type (Rosa_2007). The following publications have been ascertained in the context of this evaluation (PMID: 17192295, 22954317). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)

Comment:

Variant summary: CYP17A1 c.979_981delAAG (p.Lys327del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 4e-06 in 251444 control chromosomes. c.979_981delAAG has been reported in the literature as homozygous or compound heterozygous with another pathogenic variant in individuals affected with Congenital Adrenal Hyperplasia (Rosa_2007, Yao_2013). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% production of 17-OH progesterone (17OHP) as a measure of 17alpha-hydroxylase activity compared to wild type (Rosa_2007). The following publications have been ascertained in the context of this evaluation (PMID: 17192295, 22954317). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Targeted gene panel sequencing for molecular diagnosis of congenital adrenal hyperplasia.	Wang W	The Journal of steroid biochemistry and molecular biology	2021	PMID: 33864926
CYP17A1 mutations identified in 17 Chinese patients with 17α-hydroxylase/17,20-lyase deficiency.	Yao F	Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology	2013	PMID: 22954317
P450c17 deficiency: clinical and molecular characterization of six patients.	Rosa S	The Journal of clinical endocrinology and metabolism	2007	PMID: 17192295

Text-mined citations for this variant ...

Record last updated Aug 18, 2024

ClinVar Genomic variation as it relates to human health

NM_000102.4(CYP17A1):c.973AAG[2] (p.Lys327del)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...