NM_005027.4(PIK3R2):c.329C>G (p.Thr110Arg) AND Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 22, 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:: RCV003537681.2

Allele description [Variation Report for NM_005027.4(PIK3R2):c.329C>G (p.Thr110Arg)]

NM_005027.4(PIK3R2):c.329C>G (p.Thr110Arg)

Gene:

PIK3R2:phosphoinositide-3-kinase regulatory subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.11

Genomic location:

Preferred name:

NM_005027.4(PIK3R2):c.329C>G (p.Thr110Arg)

HGVS:

NC_000019.10:g.18160477C>G
NG_033010.2:g.12300C>G
NG_140744.1:g.198C>G
NM_005027.4:c.329C>GMANE SELECT
NP_005018.2:p.Thr110Arg
LRG_1392t1:c.329C>G
LRG_1392:g.12300C>G
LRG_1392p1:p.Thr110Arg
NC_000019.9:g.18271287C>G
NR_073517.2:n.884C>G
NR_162071.1:n.884C>G

Protein change:

T110R

Molecular consequence:

NM_005027.4:c.329C>G - missense variant - [Sequence Ontology: SO:0001583]
NR_073517.2:n.884C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_162071.1:n.884C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (MPPH1)
Synonyms:: MEGALENCEPHALY, MEGA CORPUS CALLOSUM, AND COMPLETE LACK OF MOTOR DEVELOPMENT; MEGALENCEPHALY, POLYMICROGYRIA, MEGA CORPUS CALLOSUM SYNDROME
Identifiers:: MONDO: MONDO:0011313; MedGen: C4012727; Orphanet: 83473; OMIM: 603387

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004268362	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 22, 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

SCV004268362

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 22, 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, SCV004268362.1

#	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. 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) performed at Invitae indicates that this missense variant is not expected to disrupt PIK3R2 protein function. This variant has not been reported in the literature in individuals affected with PIK3R2-related conditions. This variant is present in population databases (rs200357667, gnomAD 0.02%). This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 110 of the PIK3R2 protein (p.Thr110Arg).

#	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

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