NM_021999.5(ITM2B):c.92C>G (p.Pro31Arg) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 11, 2025
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:: RCV002040141.6

Allele description [Variation Report for NM_021999.5(ITM2B):c.92C>G (p.Pro31Arg)]

NM_021999.5(ITM2B):c.92C>G (p.Pro31Arg)

Genes:

LOC130009752:ATAC-STARR-seq lymphoblastoid silent region 5332 [Gene]
ITM2B:integral membrane protein 2B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q14.2

Genomic location:

Preferred name:

NM_021999.5(ITM2B):c.92C>G (p.Pro31Arg)

HGVS:

NC_000013.11:g.48233452C>G
NG_013069.2:g.5841C>G
NM_021999.5:c.92C>GMANE SELECT
NP_068839.1:p.Pro31Arg
LRG_1309t1:c.92C>G
LRG_1309:g.5841C>G
LRG_1309p1:p.Pro31Arg
NC_000013.10:g.48807588C>G

Protein change:

P31R

Links:

dbSNP: rs150336652

NCBI 1000 Genomes Browser:

rs150336652

Molecular consequence:

NM_021999.5:c.92C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002110122	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 11, 2025)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31719132, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002110122

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 11, 2025)

germline

clinical testing

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

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

How common are single gene mutations as a cause for lacunar stroke? A targeted gene panel study.

Tan RYY, Traylor M, Megy K, Duarte D, Deevi SVV, Shamardina O, Mapeta RP; NIHR BioResource: Rare Diseases Consortium, Ouwehand WH, Gräf S, Downes K, Markus HS.

Neurology. 2019 Nov 26;93(22):e2007-e2020. doi: 10.1212/WNL.0000000000008544. Epub 2019 Nov 12.

PubMed [citation]

PMID:: 31719132
PMCID:: PMC6913325

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, SCV002110122.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 31 of the ITM2B protein (p.Pro31Arg). This variant is present in population databases (rs150336652, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with small vessel disease stroke (PMID: 31719132). ClinVar contains an entry for this variant (Variation ID: 1353049). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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.

#	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: Feb 25, 2025

ClinVar

Relating variation to medicine