NM_006772.2(SYNGAP1):c.1861C>T (p.Arg621Ter) AND Mental retardation, autosomal dominant 5

Clinical significance:Pathogenic (Last evaluated: Sep 1, 2017)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000470395.1

Allele description

NM_006772.2(SYNGAP1):c.1861C>T (p.Arg621Ter)

Gene:
SYNGAP1:synaptic Ras GTPase activating protein 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p21.32
Genomic location:
Preferred name:
NM_006772.2(SYNGAP1):c.1861C>T (p.Arg621Ter)
HGVS:
  • NC_000006.12:g.33440913C>T
  • NG_016137.2:g.25844C>T
  • NM_006772.2:c.1861C>T
  • NP_006763.2:p.Arg621Ter
  • NC_000006.11:g.33408690C>T
Protein change:
R621*
Links:
dbSNP: rs1060503386
NCBI 1000 Genomes Browser:
rs1060503386
Molecular consequence:
  • NM_006772.2:c.1861C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Mental retardation, autosomal dominant 5 (MRD5)
Identifiers:
MedGen: C2675473; OMIM: 612621

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000552817Invitae,criteria provided, single submitter
Pathogenic
(Nov 27, 2016)
germlineclinical testing

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

SCV000807317Baylor Miraca Genetics Laboratories,criteria provided, single submitter
Pathogenic
(Sep 1, 2017)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753
See all PubMed Citations (3)

Details of each submission

From Invitae,, SCV000552817.2

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

Description

This sequence change creates a premature translational stop signal at codon 621 (p.Arg621*) of the SYNGAP1 gene. It is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in SYNGAP1 are known to be pathogenic (PMID: 23708187, 23161826). For these reasons, this variant has been classified as Pathogenic.

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

From Baylor Miraca Genetics Laboratories,, SCV000807317.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing
(GTR000508680.4)
PubMed (2)

Description

This nonsense variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory in a 7-year-old male with global delays, autistic spectrum, seizure disorder, Chiari I malformation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided
(GTR000508680.4)
not providednot providednot providednot provided

Last Updated: Nov 13, 2018

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