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NM_001382241.1(TNPO2):c.83A>G (p.Gln28Arg) AND Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 11, 2021
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:
RCV001730152.1

Allele description [Variation Report for NM_001382241.1(TNPO2):c.83A>G (p.Gln28Arg)]

NM_001382241.1(TNPO2):c.83A>G (p.Gln28Arg)

Gene:
TNPO2:transportin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.13
Genomic location:
Preferred name:
NM_001382241.1(TNPO2):c.83A>G (p.Gln28Arg)
Other names:
p.Q28R
HGVS:
  • NC_000019.10:g.12720895T>C
  • NM_001136195.2:c.83A>G
  • NM_001136196.2:c.83A>G
  • NM_001382236.1:c.83A>G
  • NM_001382237.1:c.83A>G
  • NM_001382238.1:c.83A>G
  • NM_001382239.1:c.83A>G
  • NM_001382240.1:c.83A>G
  • NM_001382241.1:c.83A>GMANE SELECT
  • NM_001382242.1:c.83A>G
  • NM_001382243.1:c.83A>G
  • NM_013433.5:c.83A>G
  • NP_001129667.1:p.Gln28Arg
  • NP_001129668.1:p.Gln28Arg
  • NP_001369165.1:p.Gln28Arg
  • NP_001369166.1:p.Gln28Arg
  • NP_001369167.1:p.Gln28Arg
  • NP_001369168.1:p.Gln28Arg
  • NP_001369169.1:p.Gln28Arg
  • NP_001369170.1:p.Gln28Arg
  • NP_001369171.1:p.Gln28Arg
  • NP_001369172.1:p.Gln28Arg
  • NP_038461.2:p.Gln28Arg
  • NC_000019.9:g.12831709T>C
  • NM_001136196.1:c.83A>G
  • NR_167974.1:n.222A>G
  • NR_167975.1:n.377A>G
  • NR_167976.1:n.377A>G
  • NR_167977.1:n.377A>G
  • NR_167978.1:n.180A>G
  • NR_167979.1:n.222A>G
Protein change:
Q28R; GLN28ARG
Links:
OMIM: 603002.0001; dbSNP: rs2145624064
NCBI 1000 Genomes Browser:
rs2145624064
Molecular consequence:
  • NM_001136195.2:c.83A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001136196.2:c.83A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382236.1:c.83A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382237.1:c.83A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382238.1:c.83A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382239.1:c.83A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382240.1:c.83A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382241.1:c.83A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382242.1:c.83A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382243.1:c.83A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_013433.5:c.83A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_167974.1:n.222A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_167975.1:n.377A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_167976.1:n.377A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_167977.1:n.377A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_167978.1:n.180A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_167979.1:n.222A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies (IDDHISD)
Identifiers:
MONDO: MONDO:0859197; MedGen: C5561997; OMIM: 619556

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001977106OMIM
no assertion criteria provided
Pathogenic
(Oct 11, 2021)
germlineliterature only

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

Summary from all submissions

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

Citations

PubMed

TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila.

Goodman LD, Cope H, Nil Z, Ravenscroft TA, Charng WL, Lu S, Tien AC, Pfundt R, Koolen DA, Haaxma CA, Veenstra-Knol HE, Wassink-Ruiter JSK, Wevers MR, Jones M, Walsh LE, Klee VH, Theunis M, Legius E, Steel D, Barwick KES, Kurian MA, Mohammad SS, et al.

Am J Hum Genet. 2021 Sep 2;108(9):1669-1691. doi: 10.1016/j.ajhg.2021.06.019. Epub 2021 Jul 26.

PubMed [citation]
PMID:
34314705
PMCID:
PMC8456166

Details of each submission

From OMIM, SCV001977106.1

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

Description

In a 6-year-old girl (patient 1) with intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies (IDDHISD; 619556), Goodman et al. (2021) identified a de novo heterozygous c.83A-G transition (c.83A-G, NM_001136196.1) in the TNPO2 gene, resulting in a gln28-to-arg (Q28R) substitution at a conserved residue in the N-terminal RAN-binding domain. The mutation, which was found by whole-exome sequencing and confirmed by Sanger sequencing, was not present in the gnomAD database. Expression of the variant in Drosophila resulted in developmental defects, including lethality, consistent with a gain-of-function effect.

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

Last Updated: May 19, 2024