NM_001360.2(DHCR7):c.704T>C (p.Phe235Ser) AND Smith-Lemli-Opitz syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Pathogenic(1);Uncertain significance(1) (Last evaluated: May 28, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000665754.2

Allele description [Variation Report for NM_001360.2(DHCR7):c.704T>C (p.Phe235Ser)]

NM_001360.2(DHCR7):c.704T>C (p.Phe235Ser)

Gene:
DHCR7:7-dehydrocholesterol reductase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q13.4
Genomic location:
Preferred name:
NM_001360.2(DHCR7):c.704T>C (p.Phe235Ser)
HGVS:
  • NC_000011.10:g.71439006A>G
  • NG_012655.2:g.14426T>C
  • NM_001163817.2:c.704T>C
  • NM_001360.2:c.704T>C
  • NP_001157289.1:p.Phe235Ser
  • NP_001351.2:p.Phe235Ser
  • LRG_340t1:c.704T>C
  • LRG_340:g.14426T>C
  • LRG_340p1:p.Phe235Ser
  • NC_000011.9:g.71150052A>G
Protein change:
F235S
Links:
dbSNP: rs1555146061
NCBI 1000 Genomes Browser:
rs1555146061
Molecular consequence:
  • NM_001163817.2:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001360.2:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Smith-Lemli-Opitz syndrome (SLOS)
Synonyms:
LETHAL ACRODYSGENITAL SYNDROME; POLYDACTYLY, SEX REVERSAL, RENAL HYPOPLASIA, AND UNILOBAR LUNG; RUTLEDGE LETHAL MULTIPLE CONGENITAL ANOMALY SYNDROME; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010035; MedGen: C0175694; Orphanet: 818; OMIM: 270400

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000789922Counsylcriteria provided, single submitter
Uncertain significance
(Feb 27, 2017)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV001588944Invitaecriteria provided, single submitter
Pathogenic
(May 28, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Residual cholesterol synthesis and simvastatin induction of cholesterol synthesis in Smith-Lemli-Opitz syndrome fibroblasts.

Wassif CA, Krakowiak PA, Wright BS, Gewandter JS, Sterner AL, Javitt N, Yergey AL, Porter FD.

Mol Genet Metab. 2005 Jun;85(2):96-107. Epub 2005 Feb 5.

PubMed [citation]
PMID:
15896653

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Counsyl, SCV000789922.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001588944.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces phenylalanine with serine at codon 235 of the DHCR7 protein (p.Phe235Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Smith-Lemli-Opitz syndrome (PMID: 15896653, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 550877). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

Support Center