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NM_006218.4(PIK3CA):c.3145G>A (p.Gly1049Ser) AND Megalencephaly-capillary malformation-polymicrogyria syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 22, 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:
RCV002051848.1

Allele description [Variation Report for NM_006218.4(PIK3CA):c.3145G>A (p.Gly1049Ser)]

NM_006218.4(PIK3CA):c.3145G>A (p.Gly1049Ser)

Gene:
PIK3CA:phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q26.32
Genomic location:
Preferred name:
NM_006218.4(PIK3CA):c.3145G>A (p.Gly1049Ser)
HGVS:
  • NC_000003.12:g.179234302G>A
  • NG_012113.2:g.90780G>A
  • NM_006218.4:c.3145G>AMANE SELECT
  • NP_006209.2:p.Gly1049Ser
  • LRG_310t1:c.3145G>A
  • LRG_310:g.90780G>A
  • NC_000003.11:g.178952090G>A
  • NM_006218.2:c.3145G>A
Protein change:
G1049S
Links:
dbSNP: rs121913277
NCBI 1000 Genomes Browser:
rs121913277
Molecular consequence:
  • NM_006218.4:c.3145G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP)
Synonyms:
Megalencephaly cutis marmorata telangiectatica congenita; Megalocephaly cutis marmorata telangiectatica congenita; Macrocephaly cutis marmorata telangiectatica congenita; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011240; MedGen: C1865285; Orphanet: 60040; OMIM: 602501

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV0023185623billion
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Mar 22, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedclinical testing

Citations

PubMed

De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.

Rivière JB, Mirzaa GM, O'Roak BJ, Beddaoui M, Alcantara D, Conway RL, St-Onge J, Schwartzentruber JA, Gripp KW, Nikkel SM, Worthylake T, Sullivan CT, Ward TR, Butler HE, Kramer NA, Albrecht B, Armour CM, Armstrong L, Caluseriu O, Cytrynbaum C, Drolet BA, Innes AM, et al.

Nat Genet. 2012 Jun 24;44(8):934-40. doi: 10.1038/ng.2331.

PubMed [citation]
PMID:
22729224
PMCID:
PMC3408813

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

Details of each submission

From 3billion, SCV002318562.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

Same or different nucleotide change resulting in same amino acid change has been previously reported to be associated with PIK3CA related disorder (ClinVar ID: VCV000376247, PMID:22729224). The variant has been previously reported as de novo in a similarly affected individual (PMID: 22729224). Different pathogenic/likely pathogenic amino acid change has been reported with supporting evidence at the same codon (ClinVar ID: VCV000376053). The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. In silico tool predictions suggest damaging effect of the variant on gene or gene product(3CNET: 0.96>=0.75). A missense variant is a common mechanism. It is not observed in the gnomAD v2.1.1 dataset. Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Mar 4, 2023