NM_000388.4(CASR):c.621del (p.Trp208fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 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:: RCV003800899.2

Allele description [Variation Report for NM_000388.4(CASR):c.621del (p.Trp208fs)]

NM_000388.4(CASR):c.621del (p.Trp208fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

3q21.1

Genomic location:

Preferred name:

NM_000388.4(CASR):c.621del (p.Trp208fs)

HGVS:

NC_000003.12:g.122261656del
NG_009058.2:g.82989del
NM_000388.4:c.621delMANE SELECT
NM_001178065.2:c.621del
NP_000379.3:p.Trp208fs
NP_001171536.2:p.Trp208fs
NC_000003.11:g.121980503del

Protein change:

W208fs

Molecular consequence:

NM_000388.4:c.621del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001178065.2:c.621del - frameshift variant - [Sequence Ontology: SO:0001589]

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

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PREDICTED: Rattus norvegicus claudin domain containing 2 (Cldnd2), transcript va...
PREDICTED: Rattus norvegicus claudin domain containing 2 (Cldnd2), transcript variant X1, mRNA
gi|2678869968|ref|XM_039087376.2|

Nucleotide
cytochrome oxidase subunit 1, partial (mitochondrion) [Leptodactylus labyrinthic...
cytochrome oxidase subunit 1, partial (mitochondrion) [Leptodactylus labyrinthicus]
gi|1074807056|gb|AOV63969.1|

Protein
zk59h03.s1 Soares_pregnant_uterus_NbHPU Homo sapiens cDNA clone IMAGE:487157 3',...
zk59h03.s1 Soares_pregnant_uterus_NbHPU Homo sapiens cDNA clone IMAGE:487157 3', mRNA sequence
gi|1523551|gnl|dbEST|661006|gb|AA04 1|

Nucleotide
RecName: Full=Ocellatin-LB2; AltName: Full=Des-Lys24-Leu25-ocellatin-F1
RecName: Full=Ocellatin-LB2; AltName: Full=Des-Lys24-Leu25-ocellatin-F1
gi|1191692567|sp|C0HKF2.1|OCE2_LEPL

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004592536	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 13, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 11807402, 14985373, 22422767, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004592536

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 13, 2023)

germline

clinical testing

PubMed (4)
[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

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

Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications.

Warner J, Epstein M, Sweet A, Singh D, Burgess J, Stranks S, Hill P, Perry-Keene D, Learoyd D, Robinson B, Birdsey P, Mackenzie E, Teh BT, Prins JB, Cardinal J.

J Med Genet. 2004 Mar;41(3):155-60.

PubMed [citation]

PMID:: 14985373
PMCID:: PMC1735699

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004592536.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with CASR-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp208Glyfs*49) in the CASR gene. It is expected to result in an absent or disrupted protein product. 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: Sep 29, 2024

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