NM_000102.4(CYP17A1):c.1247G>A (p.Arg416His) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 28, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000822737.7

Allele description [Variation Report for NM_000102.4(CYP17A1):c.1247G>A (p.Arg416His)]

NM_000102.4(CYP17A1):c.1247G>A (p.Arg416His)

Gene:

CYP17A1:cytochrome P450 family 17 subfamily A member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q24.32

Genomic location:

Preferred name:

NM_000102.4(CYP17A1):c.1247G>A (p.Arg416His)

HGVS:

NC_000010.11:g.102830982C>T
NG_007955.1:g.11552G>A
NM_000102.4:c.1247G>AMANE SELECT
NP_000093.1:p.Arg416His
NC_000010.10:g.104590739C>T
NM_000102.3:c.1247G>A

Protein change:

R416H; ARG416HIS

Links:

OMIM: 609300.0031; dbSNP: rs104894155

NCBI 1000 Genomes Browser:

rs104894155

Molecular consequence:

NM_000102.4:c.1247G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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ACAT2 [Aquila chrysaetos chrysaetos]
ACAT2 [Aquila chrysaetos chrysaetos]
Gene ID:115344254

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000963553	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 28, 2024)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 16849412, 28870780, 32784047, 17192295, 11422109, 16772352, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000963553

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 28, 2024)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Two novel mutations found in a patient with 17alpha-hydroxylase enzyme deficiency.

Ergun-Longmire B, Auchus R, Papari-Zareei M, Tansil S, Wilson RC, New MI.

J Clin Endocrinol Metab. 2006 Oct;91(10):4179-82. Epub 2006 Jul 18.

PubMed [citation]

PMID:: 16849412

Mutational analysis of rare subtypes of congenital adrenal hyperplasia in a highly inbred population.

Alswailem MM, Alzahrani OS, Alhomaidah DS, Alasmari R, Qasem E, Murugan AK, Alsagheir A, Brema I, Abbas BB, Almehthel M, Almeqbali A, Alzahrani AS.

Mol Cell Endocrinol. 2018 Feb 5;461:105-111. doi: 10.1016/j.mce.2017.08.022. Epub 2017 Sep 6.

PubMed [citation]

PMID:: 28870780

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000963553.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 416 of the CYP17A1 protein (p.Arg416His). This variant is present in population databases (rs104894155, gnomAD 0.001%). This missense change has been observed in individuals with clinical features of CYP17A1-related conditions (PMID: 16849412, 17192295, 28870780, 32784047). ClinVar contains an entry for this variant (Variation ID: 1804). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects CYP17A1 function (PMID: 17192295). This variant disrupts the p.Arg416 amino acid residue in CYP17A1. Other variant(s) that disrupt this residue have been observed in individuals with CYP17A1-related conditions (PMID: 11422109, 16772352), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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