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NM_014141.6(CNTNAP2):c.1337A>G (p.Asp446Gly) AND Cortical dysplasia-focal epilepsy syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 8, 2022
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:
RCV001852448.3

Allele description [Variation Report for NM_014141.6(CNTNAP2):c.1337A>G (p.Asp446Gly)]

NM_014141.6(CNTNAP2):c.1337A>G (p.Asp446Gly)

Gene:
CNTNAP2:contactin associated protein 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q35
Genomic location:
Preferred name:
NM_014141.6(CNTNAP2):c.1337A>G (p.Asp446Gly)
Other names:
p.D446G:GAT>GGT
HGVS:
  • NC_000007.14:g.147132498A>G
  • NG_007092.3:g.1021498A>G
  • NM_014141.6:c.1337A>GMANE SELECT
  • NP_054860.1:p.Asp446Gly
  • NC_000007.13:g.146829590A>G
  • NG_007092.2:g.1021138A>G
  • NM_014141.5:c.1337A>G
Protein change:
D446G
Links:
dbSNP: rs753860243
NCBI 1000 Genomes Browser:
rs753860243
Molecular consequence:
  • NM_014141.6:c.1337A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cortical dysplasia-focal epilepsy syndrome (PTHSL1)
Synonyms:
Pitt-Hopkins-like syndrome 1
Identifiers:
MONDO: MONDO:0012400; MedGen: C2750246; Orphanet: 221150; OMIM: 610042

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002188501Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 8, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
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. 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, SCV002188501.2

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

Description

This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 446 of the CNTNAP2 protein (p.Asp446Gly). This variant is present in population databases (rs753860243, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 205240). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.

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

Last Updated: Sep 29, 2024