NM_006772.3(SYNGAP1):c.2162T>G (p.Ile721Ser) AND Intellectual disability, autosomal dominant 5

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 24, 2023
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:: RCV000808988.7

Allele description [Variation Report for NM_006772.3(SYNGAP1):c.2162T>G (p.Ile721Ser)]

NM_006772.3(SYNGAP1):c.2162T>G (p.Ile721Ser)

Genes:

SYNGAP1-AS1:SYNGAP1 antisense RNA 1 [Gene - HGNC]
SYNGAP1:synaptic Ras GTPase activating protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.32

Genomic location:

Preferred name:

NM_006772.3(SYNGAP1):c.2162T>G (p.Ile721Ser)

HGVS:

NC_000006.12:g.33441627T>G
NG_016137.2:g.26558T>G
NM_001130066.2:c.2162T>G
NM_006772.3:c.2162T>GMANE SELECT
NP_001123538.1:p.Ile721Ser
NP_006763.2:p.Ile721Ser
LRG_1193t1:c.2162T>G
LRG_1193:g.26558T>G
LRG_1193p1:p.Ile721Ser
NC_000006.11:g.33409404T>G
NM_006772.2:c.2162T>G

Protein change:

I721S

Links:

dbSNP: rs1581993511

NCBI 1000 Genomes Browser:

rs1581993511

Molecular consequence:

NM_001130066.2:c.2162T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_006772.3:c.2162T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Intellectual disability, autosomal dominant 5 (MRD5)
Synonyms:: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 5
Identifiers:: MONDO: MONDO:0012960; MedGen: C2675473; OMIM: 612621

Recent activity

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congested-like trachea protein [Neodiprion lecontei]
congested-like trachea protein [Neodiprion lecontei]
gi|998511438|ref|XP_015516245.1|

Protein
SRX24105063 (1)
SRA
Uncultured actinomycete GT45-1 16S ribosomal RNA gene, partial sequence
Uncultured actinomycete GT45-1 16S ribosomal RNA gene, partial sequence
gi|8050786|gb|AF256039.1|

Nucleotide
Ulva ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) gene, ...
Ulva ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) gene, partial cds; chloroplast.
PopSet: 2072438586

PopSet
Ulva photosynthetic electron transfer A (petA) gene, partial cds; chloroplast.
Ulva photosynthetic electron transfer A (petA) gene, partial cds; chloroplast.
PopSet: 1918607814

PopSet

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000949122	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 24, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000949122

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 24, 2023)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000949122.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 721 of the SYNGAP1 protein (p.Ile721Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SYNGAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 653246). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SYNGAP1 protein function.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine