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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000262738	OMIM	no assertion criteria provided	Pathogenic (Mar 29, 2016)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000266514	Lupski 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)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000262738

OMIM

no assertion criteria provided

Pathogenic
(Mar 29, 2016)

germline

literature only

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

SCV000266514

Lupski 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)

germline

research

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	no	1	not provided	not provided	not provided	not provided	research

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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature 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.

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

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
2	germline	no	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Feb 14, 2024

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