NM_006306.4(SMC1A):c.1495C>T (p.Arg499Ter) AND Congenital muscular hypertrophy-cerebral syndrome

Clinical significance:Pathogenic (Last evaluated: Oct 9, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001387822.1

Allele description [Variation Report for NM_006306.4(SMC1A):c.1495C>T (p.Arg499Ter)]

NM_006306.4(SMC1A):c.1495C>T (p.Arg499Ter)

Gene:
SMC1A:structural maintenance of chromosomes 1A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp11.22
Genomic location:
Preferred name:
NM_006306.4(SMC1A):c.1495C>T (p.Arg499Ter)
HGVS:
  • NC_000023.11:g.53409112G>A
  • NG_006988.2:g.18559C>T
  • NM_001281463.1:c.1429C>T
  • NM_006306.3:c.1495C>T
  • NM_006306.4:c.1495C>TMANE SELECT
  • NP_001268392.1:p.Arg477Ter
  • NP_006297.2:p.Arg499Ter
  • NP_006297.2:p.Arg499Ter
  • LRG_773t1:c.1429C>T
  • LRG_773t2:c.1495C>T
  • LRG_773:g.18559C>T
  • LRG_773p1:p.Arg477Ter
  • LRG_773p2:p.Arg499Ter
  • NC_000023.10:g.53436043G>A
  • NC_000023.10:g.53436043G>A
  • NM_006306.2:c.1495C>T
Protein change:
R477*
Links:
dbSNP: rs1556890135
NCBI 1000 Genomes Browser:
rs1556890135
Molecular consequence:
  • NM_001281463.1:c.1429C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_006306.3:c.1495C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_006306.4:c.1495C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Congenital muscular hypertrophy-cerebral syndrome (CDLS2)
Synonyms:
Cornelia de Lange syndrome 2
Identifiers:
MONDO: MONDO:0010370; MedGen: C1802395; Orphanet: 199; OMIM: 300590

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001588541Invitaecriteria provided, single submitter
Pathogenic
(Oct 9, 2020)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A novel nonsense SMC1A mutation in a patient with intractable epilepsy and cardiac malformation.

Chinen Y, Nakamura S, Kaneshi T, Nakayashiro M, Yanagi K, Kaname T, Naritomi K, Nakanishi K.

Hum Genome Var. 2019;6:23. doi: 10.1038/s41439-019-0053-y.

PubMed [citation]
PMID:
31098032
PMCID:
PMC6513828

Novel SMC1A frameshift mutations in children with developmental delay and epilepsy.

Goldstein JH, Tim-Aroon T, Shieh J, Merrill M, Deeb KK, Zhang S, Bass NE, Bedoyan JK.

Eur J Med Genet. 2015 Oct;58(10):562-8. doi: 10.1016/j.ejmg.2015.09.007. Epub 2015 Sep 18.

PubMed [citation]
PMID:
26386245
See all PubMed Citations (7)

Details of each submission

From Invitae, SCV001588541.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Arg499*) in the SMC1A gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with SMC1A-related conditions (PMID: 31098032, 31334757). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 489224). Loss-of-function variants in SMC1A are known to be pathogenic (PMID: 26386245, 27334371, 28166369, 28548707, 31334757). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 25, 2021

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