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NM_001360.3(DHCR7):c.376G>A (p.Val126Ile) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 13, 2023
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:
RCV003488428.1

Allele description [Variation Report for NM_001360.3(DHCR7):c.376G>A (p.Val126Ile)]

NM_001360.3(DHCR7):c.376G>A (p.Val126Ile)

Genes:
NADSYN1:NAD synthetase 1 [Gene - OMIM - HGNC]
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.376G>A (p.Val126Ile)
HGVS:
  • NC_000011.10:g.71442299C>T
  • NG_012655.2:g.11133G>A
  • NM_001163817.2:c.376G>A
  • NM_001360.3:c.376G>AMANE SELECT
  • NP_001157289.1:p.Val126Ile
  • NP_001351.2:p.Val126Ile
  • NP_001351.2:p.Val126Ile
  • LRG_340t1:c.376G>A
  • LRG_340:g.11133G>A
  • LRG_340p1:p.Val126Ile
  • NC_000011.9:g.71153345C>T
  • NM_001360.2:c.376G>A
Protein change:
V126I
Links:
dbSNP: rs143587828
NCBI 1000 Genomes Browser:
rs143587828
Molecular consequence:
  • NM_001163817.2:c.376G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001360.3:c.376G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004241064Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Dec 13, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Prevalence of four Mendelian disorders associated with autism in 2392 affected families.

Saskin A, Fulginiti V, Birch AH, Trakadis Y.

J Hum Genet. 2017 Jun;62(6):657-659. doi: 10.1038/jhg.2017.16. Epub 2017 Mar 9.

PubMed [citation]
PMID:
28250423

Determination of the allelic frequency in Smith-Lemli-Opitz syndrome by analysis of massively parallel sequencing data sets.

Cross JL, Iben J, Simpson CL, Thurm A, Swedo S, Tierney E, Bailey-Wilson JE, Biesecker LG, Porter FD, Wassif CA.

Clin Genet. 2015 Jun;87(6):570-5. doi: 10.1111/cge.12425. Epub 2014 Jun 6.

PubMed [citation]
PMID:
24813812
PMCID:
PMC4225182
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004241064.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: DHCR7 c.376G>A (p.Val126Ile) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 250706 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in DHCR7 causing Smith-Lemli-Opitz Syndrome (0.00012 vs 0.0043), allowing no conclusion about variant significance. c.376G>A has been reported in the literature in a homozygous 12 months old dysmorphic male with microcephaly, and strabismus (example: Monies_2019). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 34168679, 24813812, 31130284, 28250423). Nine submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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

Last Updated: Nov 3, 2024