NM_022489.4(INF2):c.550G>A (p.Glu184Lys) AND multiple conditions

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 15, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001535996.9

Allele description [Variation Report for NM_022489.4(INF2):c.550G>A (p.Glu184Lys)]

NM_022489.4(INF2):c.550G>A (p.Glu184Lys)

Gene:

INF2:inverted formin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q32.33

Genomic location:

Preferred name:

NM_022489.4(INF2):c.550G>A (p.Glu184Lys)

HGVS:

NC_000014.9:g.104703337G>A
NG_027684.1:g.18732G>A
NM_001031714.4:c.550G>A
NM_022489.4:c.550G>AMANE SELECT
NM_032714.3:c.550G>A
NP_001026884.3:p.Glu184Lys
NP_071934.3:p.Glu184Lys
NP_116103.1:p.Glu184Lys
NC_000014.8:g.105169674G>A
NM_022489.3:c.550G>A

Protein change:

E184K

Links:

dbSNP: rs1566778676

NCBI 1000 Genomes Browser:

rs1566778676

Molecular consequence:

NM_001031714.4:c.550G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022489.4:c.550G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_032714.3:c.550G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Focal segmental glomerulosclerosis 5 (FSGS5)
Identifiers:: MONDO: MONDO:0013191; MedGen: C2750475; Orphanet: 656; OMIM: 613237

Name:: Charcot-Marie-Tooth disease dominant intermediate E
Synonyms:: CHARCOT-MARIE-TOOTH NEUROPATHY WITH FOCAL SEGMENTAL GLOMERULONEPHRITIS
Identifiers:: MONDO: MONDO:0013758; MedGen: C4302667; Orphanet: 93114; OMIM: 614455

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BE800884 (0)
MeSH
ARHGAP18 [Bos mutus]
ARHGAP18 [Bos mutus]
Gene ID:102283538

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001752669	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 23, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002228604	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 15, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 25165188, 25676889, 26467726, 20023659, 26086034, 26764407, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001752669

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 23, 2022)

unknown

clinical testing

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

SCV002228604

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 15, 2022)

germline

clinical testing

PubMed (7)
[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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Novel INF2 mutations in an Italian cohort of patients with focal segmental glomerulosclerosis, renal failure and Charcot-Marie-Tooth neuropathy.

Caridi G, Lugani F, Dagnino M, Gigante M, Iolascon A, Falco M, Graziano C, Benetti E, Dugo M, Del Prete D, Granata A, Borracelli D, Moggia E, Quaglia M, Rinaldi R, Gesualdo L, Ghiggeri GM.

Nephrol Dial Transplant. 2014 Sep;29 Suppl 4:iv80-6. doi: 10.1093/ndt/gfu071.

PubMed [citation]

PMID:: 25165188

See all PubMed Citations (8)

Details of each submission

From Fulgent Genetics, Fulgent Genetics, SCV001752669.2

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002228604.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 184 of the INF2 protein (p.Glu184Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with focal segmental glomerulosclerosis and Charcot-Marie-Tooth disease (PMID: 20023659, 25165188, 25676889, 26467726). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 599128). 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 expected to disrupt INF2 protein function. Experimental studies have shown that this missense change affects INF2 function (PMID: 20023659, 26086034, 26764407). For these reasons, this variant has been classified as Pathogenic.

#	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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