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NM_014491.4(FOXP2):c.982C>T (p.Arg328Ter) AND Speech-language disorder 1

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Mar 2, 2016
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000005372.3

Allele description

NM_014491.4(FOXP2):c.982C>T (p.Arg328Ter)

Gene:
FOXP2:forkhead box P2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q31.1
Genomic location:
Preferred name:
NM_014491.4(FOXP2):c.982C>T (p.Arg328Ter)
HGVS:
  • NC_000007.14:g.114642616C>T
  • NG_007491.2:g.561307C>T
  • NG_007491.3:g.561307C>T
  • NM_001172766.3:c.979C>T
  • NM_001172767.2:c.1057C>T
  • NM_014491.4:c.982C>T
  • NM_148898.4:c.1057C>T
  • NM_148899.3:c.982C>T
  • NM_148900.3:c.1033C>T
  • NP_001166237.1:p.Arg327Ter
  • NP_001166238.1:p.Arg353Ter
  • NP_055306.1:p.Arg328Ter
  • NP_055306.1:p.Arg328Ter
  • NP_683696.2:p.Arg353Ter
  • NP_683697.2:p.Arg328Ter
  • NP_683698.2:p.Arg345Ter
  • NC_000007.13:g.114282671C>T
  • NM_014491.3:c.982C>T
  • NR_033766.2:n.1552C>T
  • NR_033767.2:n.1596C>T
Protein change:
R327*; ARG328TER
Links:
OMIM: 605317.0002; dbSNP: rs121908378
NCBI 1000 Genomes Browser:
rs121908378
Molecular consequence:
  • NR_033766.2:n.1552C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_033767.2:n.1596C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001172766.3:c.979C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001172767.2:c.1057C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_014491.4:c.982C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_148898.4:c.1057C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_148899.3:c.982C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_148900.3:c.1033C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Speech-language disorder 1 (SPCH1)
Synonyms:
DEVELOPMENTAL VERBAL DYSPRAXIA; SPEECH AND LANGUAGE DISORDER WITH OROFACIAL DYSPRAXIA; CHILDHOOD APRAXIA OF SPEECH
Identifiers:
MONDO: MONDO:0011184; MedGen: C0750927; Orphanet: 209908; OMIM: 602081

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000025552OMIM
no assertion criteria provided
Pathogenic
(Jul 1, 2012) 		germlineliterature only

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

SCV000292265GeneReviews
no assertion criteria provided
Pathogenic
(Mar 2, 2016) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
Caucasiangermlineyes3not providednot providednot providednot providedliterature only

Citations

PubMed

The DISC1 promoter: characterization and regulation by FOXP2.

Walker RM, Hill AE, Newman AC, Hamilton G, Torrance HS, Anderson SM, Ogawa F, Derizioti P, Nicod J, Vernes SC, Fisher SE, Thomson PA, Porteous DJ, Evans KL.

Hum Mol Genet. 2012 Jul 1;21(13):2862-72. doi: 10.1093/hmg/dds111. Epub 2012 Mar 20.

PubMed [citation]
PMID:
22434823

Identification of FOXP2 truncation as a novel cause of developmental speech and language deficits.

MacDermot KD, Bonora E, Sykes N, Coupe AM, Lai CS, Vernes SC, Vargha-Khadem F, McKenzie F, Smith RL, Monaco AP, Fisher SE.

Am J Hum Genet. 2005 Jun;76(6):1074-80. Epub 2005 Apr 22.

PubMed [citation]
PMID:
15877281
PMCID:
PMC1196445

Details of each submission

From OMIM, SCV000025552.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In 2 sibs with verbal dyspraxia (602081), MacDermot et al. (2005) identified a heterozygous C-to-T transition in exon 7 of the FOXP2 gene, resulting in an arg328-to-ter (R328X) substitution. The mother, who had a history of speech problems, also carried the mutation, whereas the unaffected father did not. The R328X mutation was not identified in 252 control chromosomes. The R328X mutation is predicted to yield a truncated protein product lacking the zinc finger, leucine zipper, and forkhead DNA-binding domains.

Walker et al. (2012) found that the R328X mutation reduced the ability of FOXP2 to downregulate DISC1 (605210).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From GeneReviews, SCV000292265.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Caucasian3not providednot providedliterature only PubMed (1)

Description

Speech: CAS / Non-verbal / Poor clarity Oromotor: Oropharyngeal dyspraxia Language: Impaired expressive & receptive / Simple grammar Cognition: Comprehension difficulties Other: Motor dyspraxia

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided3not providednot providednot provided

Last Updated: Jun 15, 2020