NM_003672.4(CDC14A):c.1126C>T (p.Arg376Ter) AND Autosomal recessive nonsyndromic hearing loss 32

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 5, 2018
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:: RCV000223951.12

Allele description [Variation Report for NM_003672.4(CDC14A):c.1126C>T (p.Arg376Ter)]

NM_003672.4(CDC14A):c.1126C>T (p.Arg376Ter)

Gene:

CDC14A:cell division cycle 14A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p21.2

Genomic location:

Preferred name:

NM_003672.4(CDC14A):c.1126C>T (p.Arg376Ter)

HGVS:

NC_000001.11:g.100484440C>T
NG_051602.2:g.144440C>T
NM_001319210.2:c.1126C>T
NM_001319211.2:c.952C>T
NM_001319212.2:c.247C>T
NM_003672.4:c.1126C>TMANE SELECT
NM_033312.3:c.1126C>T
NM_033313.3:c.1126C>T
NP_001306139.1:p.Arg376Ter
NP_001306140.1:p.Arg318Ter
NP_001306141.1:p.Arg83Ter
NP_003663.2:p.Arg376Ter
NP_201569.1:p.Arg376Ter
NP_201569.1:p.Arg376Ter
NP_201570.1:p.Arg376Ter
LRG_1418t1:c.1126C>T
LRG_1418:g.144440C>T
LRG_1418p1:p.Arg376Ter
NC_000001.10:g.100949996C>T
NM_003672.3:c.1126C>T
NM_033312.2:c.1126C>T

Protein change:

R318*; ARG376TER

Links:

OMIM: 603504.0001; dbSNP: rs876661408

NCBI 1000 Genomes Browser:

rs876661408

Molecular consequence:

NM_001319210.2:c.1126C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001319211.2:c.952C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001319212.2:c.247C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_003672.4:c.1126C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_033312.3:c.1126C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_033313.3:c.1126C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Autosomal recessive nonsyndromic hearing loss 32
Synonyms:: Deafness, autosomal recessive 32; Deafness, autosomal recessive 105
Identifiers:: MONDO: MONDO:0012091; MedGen: C1837608; Orphanet: 90636; OMIM: 608653

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
SCV000280584	OMIM	no assertion criteria provided	Pathogenic (Aug 3, 2018)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 27259055, 29293958
SCV000930075	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 5, 2018)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 29293958, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000280584

OMIM

no assertion criteria provided

Pathogenic
(Aug 3, 2018)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000930075

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 5, 2018)

unknown

curation

PubMed (2)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutations in CDC14A, Encoding a Protein Phosphatase Involved in Hair Cell Ciliogenesis, Cause Autosomal-Recessive Severe to Profound Deafness.

Delmaghani S, Aghaie A, Bouyacoub Y, El Hachmi H, Bonnet C, Riahi Z, Chardenoux S, Perfettini I, Hardelin JP, Houmeida A, Herbomel P, Petit C.

Am J Hum Genet. 2016 Jun 2;98(6):1266-1270. doi: 10.1016/j.ajhg.2016.04.015.

PubMed [citation]

PMID:: 27259055
PMCID:: PMC4908234

CDC14A phosphatase is essential for hearing and male fertility in mouse and human.

Imtiaz A, Belyantseva IA, Beirl AJ, Fenollar-Ferrer C, Bashir R, Bukhari I, Bouzid A, Shaukat U, Azaiez H, Booth KT, Kahrizi K, Najmabadi H, Maqsood A, Wilson EA, Fitzgerald TS, Tlili A, Olszewski R, Lund M, Chaudhry T, Rehman AU, Starost MF, Waryah AM, et al.

Hum Mol Genet. 2018 Mar 1;27(5):780-798. doi: 10.1093/hmg/ddx440.

PubMed [citation]

PMID:: 29293958
PMCID:: PMC6059191

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000280584.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In affected members of a consanguineous Iranian family with severe prelingual deafness (DFNB32; 608653), Delmaghani et al. (2016) identified homozygosity for a c.1126C-T transition (c.1126C-T, NM_033312.2) in exon 11 of the CDC14A gene, resulting in an arg376-to-ter (R376X) substitution. The mutation segregated fully with disease in the family and was not found in 150 Iranian controls or in the 1000 Genomes Project or Exome Variant Server databases. The reported pedigree included a deaf man with an obligate carrier daughter, who entered into a consanguineous marriage and had 2 deaf children.

Imtiaz et al. (2018) reported a consanguineous Iranian family (MORL2) in which 2 sisters and a brother had autosomal recessive prelingual sensorineural moderate to profound hearing loss due to homozygosity for the R376X mutation. The deaf brother had a biologic son.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From SIB Swiss Institute of Bioinformatics, SCV000930075.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)

Description

This variant is interpreted as a Pathogenic for Deafness, autosomal recessive 32, with or without immotile sperm. The following ACMG Tag(s) were applied: PM2 : Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PVS1-Strong : PVS1 downgraded in strength to Strong. PP1-Strong : Segregation data PP1 upgraded to strong (PMID:29293958).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 1, 2024

ClinVar

Relating variation to medicine