NM_001360.3(DHCR7):c.866C>T (p.Thr289Ile) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Feb 22, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000412788.7

Allele description [Variation Report for NM_001360.3(DHCR7):c.866C>T (p.Thr289Ile)]

NM_001360.3(DHCR7):c.866C>T (p.Thr289Ile)

Gene:

DHCR7:7-dehydrocholesterol reductase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.4

Genomic location:

Preferred name:

NM_001360.3(DHCR7):c.866C>T (p.Thr289Ile)

HGVS:

NC_000011.10:g.71437909G>A
NG_012655.2:g.15523C>T
NM_001163817.2:c.866C>T
NM_001360.3:c.866C>TMANE SELECT
NP_001157289.1:p.Thr289Ile
NP_001351.2:p.Thr289Ile
NP_001351.2:p.Thr289Ile
LRG_340t1:c.866C>T
LRG_340:g.15523C>T
LRG_340p1:p.Thr289Ile
NC_000011.9:g.71148955G>A
NM_001360.2:c.866C>T
Q9UBM7:p.Thr289Ile

Protein change:

T289I; THR289ILE

Links:

UniProtKB: Q9UBM7#VAR_012725; OMIM: 602858.0015; dbSNP: rs121909765

NCBI 1000 Genomes Browser:

rs121909765

Molecular consequence:

NM_001163817.2:c.866C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001360.3:c.866C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000490514	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 22, 2022)	germline	clinical testing	Citation Link,
SCV001143731	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics criteria)	Likely pathogenic (Sep 21, 2020)	unknown	clinical testing	PubMed (13) [See all records that cite these PMIDs] 9714007, 11111101, 11186897, 11471166, 24500076, 10677299, 10995508, 11298379, 12070263, 29300326, 23603282, 11175299, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000490514

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Feb 22, 2022)

germline

clinical testing

Citation Link,

SCV001143731

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics criteria)

Likely pathogenic
(Sep 21, 2020)

unknown

clinical testing

PubMed (13)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Smith-Lemli-Opitz syndrome: phenotypic extreme with minimal clinical findings.

Nowaczyk MJ, Whelan DT, Hill RE.

Am J Med Genet. 1998 Aug 6;78(5):419-23.

PubMed [citation]

PMID:: 9714007

Biochemical and genetic aspects of 7-dehydrocholesterol reductase and Smith-Lemli-Opitz syndrome.

Waterham HR, Wanders RJ.

Biochim Biophys Acta. 2000 Dec 15;1529(1-3):340-56. Review.

PubMed [citation]

PMID:: 11111101

See all PubMed Citations (13)

Details of each submission

From GeneDx, SCV000490514.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29300326, 11111101, 12914579, 16392899, 24500076, 11298379, 9714007, 10995508, 11186897, 11471166, 23603282, 12070263)

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

From Athena Diagnostics, SCV001143731.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (13)

Description

The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant appears to segregate with disease in at least one family, however, the available information does not rule out segregation due to chance. Assessment of experimental evidence suggests this variant results in abnormal protein function. Elevated levels of 7-DHC were present in patients (PMID: 9714007).

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

Last Updated: Sep 29, 2024

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