VCV000618692.20 - ClinVar

NM_022489.4(INF2):c.609C>T (p.Ala203=)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(4)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_022489.4(INF2):c.609C>T (p.Ala203=)

Variation ID: 618692 Accession: VCV000618692.20

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 14q32.33 14: 104703396 (GRCh38) [ NCBI UCSC ] 14: 105169733 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Feb 18, 2019	Feb 28, 2024	Jul 28, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_022489.4:c.609C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_071934.3:p.Ala203=	synonymous
NM_001031714.4:c.609C>T	NP_001026884.3:p.Ala203=	synonymous
NM_032714.3:c.609C>T	NP_116103.1:p.Ala203=	synonymous
NC_000014.9:g.104703396C>T
NC_000014.8:g.105169733C>T
NG_027684.1:g.18791C>T

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000014.9:104703395:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00020 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

Exome Aggregation Consortium (ExAC) 0.00012

The Genome Aggregation Database (gnomAD), exomes 0.00014

1000 Genomes Project 30x 0.00016

Trans-Omics for Precision Medicine (TOPMed) 0.00019

1000 Genomes Project 0.00020

The Genome Aggregation Database (gnomAD) 0.00028

Links

dbSNP: rs140017506 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
INF2		-	-	GRCh38 GRCh37	1478	1566

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Likely benign (1)	criteria provided, single submitter	Feb 15, 2018	RCV000757411.11
Charcot-Marie-Tooth disease dominant intermediate E Focal segmental glomerulosclerosis 5	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Jul 28, 2023	RCV001078553.8
Focal segmental glomerulosclerosis 5	Benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV001113743.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely benign (Feb 15, 2018)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process) Method: clinical testing	Not Provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000885620.1 First in ClinVar: Feb 18, 2019 Last updated: Feb 18, 2019	Comment: The c.609C>T; p.Ala203Ala variant (rs140017506) does not alter the amino acid sequence of the INF2 protein and computational splice site prediction algorithms do not predict … (more) The c.609C>T; p.Ala203Ala variant (rs140017506) does not alter the amino acid sequence of the INF2 protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site. This variant has not been reported in association with CMT in medical literature or in gene specific variation databases. This variant is listed in the genome Aggregation Database (gnomAD) with a Finnish population frequency of 0.1% (identified on 26 out of 25,772 chromosomes). Based on the available information, the c.609C>T variant is likely to be benign. (less)
Benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Focal segmental glomerulosclerosis 5 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001271535.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
Likely benign (Jan 08, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Focal segmental glomerulosclerosis 5 Charcot-Marie-Tooth disease dominant intermediate E Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002795627.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Benign (Jul 28, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Charcot-Marie-Tooth disease dominant intermediate E Focal segmental glomerulosclerosis 5 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001019626.5 First in ClinVar: Dec 17, 2019 Last updated: Feb 28, 2024

Comment:

The c.609C>T; p.Ala203Ala variant (rs140017506) does not alter the amino acid sequence of the INF2 protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site. This variant has not been reported in association with CMT in medical literature or in gene specific variation databases. This variant is listed in the genome Aggregation Database (gnomAD) with a Finnish population frequency of 0.1% (identified on 26 out of 25,772 chromosomes). Based on the available information, the c.609C>T variant is likely to be benign.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs140017506 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_022489.4(INF2):c.609C>T (p.Ala203=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs140017506 ...