NM_000388.4(CASR):c.1377+1G>A AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jun 24, 2022
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:: RCV003033614.2

Allele description

NM_000388.4(CASR):c.1377+1G>A

Gene:

CASR:calcium sensing receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q21.1

Genomic location:

Preferred name:

NM_000388.4(CASR):c.1377+1G>A

HGVS:

NC_000003.12:g.122262413G>A
NG_009058.2:g.83746G>A
NM_000388.4:c.1377+1G>AMANE SELECT
NM_001178065.2:c.1377+1G>A
NC_000003.11:g.121981260G>A

Molecular consequence:

NM_000388.4:c.1377+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001178065.2:c.1377+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Familial hypocalciuric hypercalcemia (FHH)
Synonyms:: Familial benign hypercalcemia
Identifiers:: MONDO: MONDO:0018458; MedGen: C1809471; OMIM: PS145980

Name:: Autosomal dominant hypocalcemia 1 (HYPOC1)
Synonyms:: HYPOCALCEMIA, FAMILIAL
Identifiers:: MONDO: MONDO:0011013; MedGen: C0342345; OMIM: 601198

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003322625	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 24, 2022)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 32347971, 16199547, 11807402, 14985373, 22422767, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003322625

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 24, 2022)

germline

clinical testing

PubMed (6)
[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

Clinical characteristics of familial hypocalciuric hypercalcaemia type 1: A multicentre study of 77 adult patients.

Mouly C, Vargas-Poussou R, Lienhardt A, Silve C, Hureaux M, Magdelaine C, Buffet A, Grunenwald S, Kuhn JM, Brue T, Reznik Y, Tabarin A, Martin-Coignard D, Haymann JP, Tack I, Bennet A, Caron P, Linglart A, Vezzosi D; Reference Centre for Rare Diseases of Calcium, Phosphate Metabolism..

Clin Endocrinol (Oxf). 2020 Sep;93(3):248-260. doi: 10.1111/cen.14211. Epub 2020 May 14.

PubMed [citation]

PMID:: 32347971

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 (6)

Details of each submission

From Invitae, SCV003322625.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

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. Disruption of this splice site has been observed in individual(s) with clinical features of familial hypocalciuric hypercalcaemia (PMID: 32347971). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 4 of the CASR 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 CASR are known to be pathogenic (PMID: 11807402, 14985373, 22422767).

#	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: Feb 28, 2024

ClinVar

Relating variation to medicine