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NM_001371986.1(UNC80):c.5296C>T (p.Pro1766Ser) AND Hypotonia, infantile, with psychomotor retardation and characteristic facies 2

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Jan 7, 2016
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:
RCV000207456.4

Allele description [Variation Report for NM_001371986.1(UNC80):c.5296C>T (p.Pro1766Ser)]

NM_001371986.1(UNC80):c.5296C>T (p.Pro1766Ser)

Genes:
LOC126806490:P300/CBP strongly-dependent group 1 enhancer GRCh37_chr2:210782411-210783610 [Gene]
UNC80:unc-80 homolog, NALCN channel complex subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q34
Genomic location:
Preferred name:
NM_001371986.1(UNC80):c.5296C>T (p.Pro1766Ser)
HGVS:
  • NC_000002.12:g.209918616C>T
  • NG_051361.1:g.151692C>T
  • NM_001371986.1:c.5296C>TMANE SELECT
  • NM_032504.2:c.5098C>T
  • NM_182587.4:c.5083C>T
  • NP_001358915.1:p.Pro1766Ser
  • NP_115893.1:p.Pro1700Ser
  • NP_115893.1:p.Pro1700Ser
  • NP_872393.3:p.Pro1695Ser
  • NC_000002.11:g.210783340C>T
  • NM_032504.1:c.5098C>T
  • Q8N2C7:p.Pro1700Ser
Protein change:
P1695S; PRO1700SER
Links:
UniProtKB: Q8N2C7#VAR_075875; OMIM: 612636.0001; dbSNP: rs869025316
NCBI 1000 Genomes Browser:
rs869025316
Molecular consequence:
  • NM_001371986.1:c.5296C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_032504.2:c.5098C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_182587.4:c.5083C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypotonia, infantile, with psychomotor retardation and characteristic facies 2 (IHPRF2)
Identifiers:
MONDO: MONDO:0014777; MedGen: C4225203; Orphanet: 371364; OMIM: 616801

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000262738OMIM
no assertion criteria provided
Pathogenic
(Mar 29, 2016) 		germlineliterature only

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

SCV000266514Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine
criteria provided, single submitter

(Stray-Pedersen et al. (Am J Hum Genet 2016))		Likely pathogenic
(Jan 7, 2016) 		germlineresearch

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineno1not providednot providednot providednot providedresearch
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineyes1not providednot providednot providednot providedresearch

Citations

PubMed

Biallelic Mutations in UNC80 Cause Persistent Hypotonia, Encephalopathy, Growth Retardation, and Severe Intellectual Disability.

Stray-Pedersen A, Cobben JM, Prescott TE, Lee S, Cang C, Aranda K, Ahmed S, Alders M, Gerstner T, Aslaksen K, Tétreault M, Qin W, Hartley T, Jhangiani SN, Muzny DM, Tarailo-Graovac M, van Karnebeek CD; Care4Rare Canada Consortium.; Baylor-Hopkins Center for Mendelian Genomics., Lupski JR, Ren D, Yoon G.

Am J Hum Genet. 2016 Jan 7;98(1):202-9. doi: 10.1016/j.ajhg.2015.11.004. Epub 2015 Dec 17.

PubMed [citation]
PMID:
26708751
PMCID:
PMC4716670

Details of each submission

From OMIM, SCV000262738.2

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

Description

In a 4-year-old girl, born of consanguineous Iraqi parents, with infantile hypotonia with psychomotor retardation and characteristic facies-2 (IHPRF2; 616801), Stray-Pedersen et al. (2016) identified a homozygous c.5098C-T transition (c.5098C-T, NM_032504.1) in exon 32 of the UNC80 gene, resulting in a pro1700-to-ser (P1700S) substitution at a highly conserved residue. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not found in the dbSNP, 1000 Genomes Project, or ExAC databases, but was present in heterozygous state in 1 of over 3,000 in-house control exomes. The unaffected mother carried the mutation; DNA from the father was not available. Transfection of the mutation into the mouse gene and HEK293T cells showed that it was expressed normally and associated with UNC79 (616884) and NALCN (611549), but patch-clamp recording studies showed that the variant had significantly reduced NALCN currents compared to wildtype, consistent with a loss of function.

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

From Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine, SCV000266514.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedresearch PubMed (1)
2not provided1not providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided
2germlinenonot providednot providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024