NM_000785.4(CYP27B1):c.196-2A>G AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 20, 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:: RCV001227842.8

Allele description [Variation Report for NM_000785.4(CYP27B1):c.196-2A>G]

NM_000785.4(CYP27B1):c.196-2A>G

Gene:

CYP27B1:cytochrome P450 family 27 subfamily B member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q14.1

Genomic location:

Preferred name:

NM_000785.4(CYP27B1):c.196-2A>G

HGVS:

NC_000012.12:g.57766199T>C
NG_007076.1:g.5995A>G
NM_000785.4:c.196-2A>GMANE SELECT
NC_000012.11:g.58159982T>C
NM_000785.3:c.196-2A>G

Links:

dbSNP: rs772960103

NCBI 1000 Genomes Browser:

rs772960103

Molecular consequence:

NM_000785.4:c.196-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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LOC127265710 [Andrographis paniculata]
LOC127265710 [Andrographis paniculata]
Gene ID:127265710

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001400218	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Mar 20, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 36321535, 16199547, 9837822, 17488797, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001400218

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Mar 20, 2023)

germline

clinical testing

PubMed (5)
[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

Genotype-phenotype Description of Vitamin D-dependent Rickets 1A: CYP27B1 p.(Ala129Thr) Variant Induces a Milder Disease.

Méaux MN, Harambat J, Rothenbuhler A, Léger J, Kamenicky P, Soskin S, Boyer O, Boros E, D'Anella P, Mignot B, Gebhart M, Vic P, Richard N, Thivichon-Prince B, Francou B, Linglart A, Bacchetta J, Molin A.

J Clin Endocrinol Metab. 2023 Mar 10;108(4):812-826. doi: 10.1210/clinem/dgac639.

PubMed [citation]

PMID:: 36321535

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001400218.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Disruption of this splice site has been observed in individual(s) with clinical features of vitamin-D dependent rickets (PMID: 36321535). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 955237). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change affects an acceptor splice site in intron 1 of the CYP27B1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CYP27B1 are known to be pathogenic (PMID: 9837822, 17488797).

#	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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