NM_000388.4(CASR):c.186-1G>T AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 15, 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:: RCV001390066.12

Allele description [Variation Report for NM_000388.4(CASR):c.186-1G>T]

NM_000388.4(CASR):c.186-1G>T

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.186-1G>T

HGVS:

NC_000003.12:g.122257080G>T
NG_009058.2:g.78413G>T
NM_000388.4:c.186-1G>TMANE SELECT
NM_001178065.2:c.186-1G>T
NC_000003.11:g.121975927G>T
NM_000388.3:c.186-1G>T

Note:

NCBI staff reviewed the sequence information reported in PubMed 11668634 Fig. 5 to determine the location of this allele on the current reference sequence.

Nucleotide change:

IVS2AS, G-T, -1

Links:

OMIM: 601199.0033; dbSNP: rs797044441

NCBI 1000 Genomes Browser:

rs797044441

Molecular consequence:

NM_000388.4:c.186-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001178065.2:c.186-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001591668	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 15, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 16199547, 11807402, 14985373, 22422767, 11668634, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001591668

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 15, 2023)

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

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

Familial isolated hyperparathyroidism: clinical and genetic characteristics of 36 kindreds.

Simonds WF, James-Newton LA, Agarwal SK, Yang B, Skarulis MC, Hendy GN, Marx SJ.

Medicine (Baltimore). 2002 Jan;81(1):1-26. Review. No abstract available.

PubMed [citation]

PMID:: 11807402

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001591668.4

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

Description

This sequence change affects an acceptor splice site in intron 2 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with hypocalciuric hypercalcemia (PMID: 11668634). ClinVar contains an entry for this variant (Variation ID: 8342). Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 11668634). For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 26, 2024

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