VCV000225144.23 - ClinVar

NM_014625.4(NPHS2):c.-51G>T

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.

(13)

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

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

This variant is part of a Haplotype

NM_014625.3(NPHS2):c.[-52C>G(;)-51G>T]

Identifiers

NM_014625.4(NPHS2):c.-51G>T

Variation ID: 225144 Accession: VCV000225144.23

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q25.2 1: 179575915 (GRCh38) [ NCBI UCSC ] 1: 179545050 (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	Apr 14, 2016	Oct 8, 2024	Jul 15, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_014625.4:c.-51G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		5 prime UTR
NM_001297575.2:c.-51G>T		5 prime UTR
NC_000001.11:g.179575915C>A
NC_000001.10:g.179545050C>A
NG_007535.1:g.5035G>T
LRG_887:g.5035G>T
LRG_887t1:c.-51G>T

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000001.11:179575914:C:A

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.

0.18331 (A)

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

1000 Genomes Project 0.18331

1000 Genomes Project 30x 0.18348

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.19314

Trans-Omics for Precision Medicine (TOPMed) 0.23152

The Genome Aggregation Database (gnomAD) 0.23878

The Genome Aggregation Database (gnomAD), exomes 0.25451

Exome Aggregation Consortium (ExAC) 0.36538

Links

dbSNP: rs12406197 ClinGen: CA354148 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.
NPHS2		-	-	GRCh38 GRCh37	346	561

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.
Nephrotic syndrome, type 2	Benign (3)	criteria provided, multiple submitters, no conflicts	May 18, 2021	RCV000210804.9
not specified	Benign (5)	criteria provided, multiple submitters, no conflicts	Jul 15, 2024	RCV001354810.6
Focal segmental glomerulosclerosis	Benign (1)	criteria provided, single submitter	Sep 27, 2022	RCV002294081.2
not provided	Benign (3)	criteria provided, multiple submitters, no conflicts	Jan 22, 2024	RCV001513259.8
NPHS2-related disorder	Benign (1)	no assertion criteria provided	Feb 23, 2021	RCV003982952.2

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.
Benign (Mar 06, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Nephrotic syndrome, type 2 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000351511.3 First in ClinVar: Dec 06, 2016 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)
Benign (May 18, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Nephrotic syndrome, type 2 Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001737189.1 First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021	Sex: mixed
Benign (May 04, 2022)	criteria provided, single submitter (Mendelics Assertion Criteria 2019) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Mendelics Accession: SCV002517764.1 First in ClinVar: May 28, 2022 Last updated: May 28, 2022
Benign (Nov 20, 2019)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001950627.2 First in ClinVar: Oct 02, 2021 Last updated: Mar 04, 2023	Comment: This variant is associated with the following publications: (PMID: 16900088, 30793612)
Benign (Jan 22, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001720851.3 First in ClinVar: Jun 15, 2021 Last updated: Feb 14, 2024
Benign (Sep 27, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Inherited focal segmental glomerulosclerosis Affected status: unknown Allele origin: germline	Genome Diagnostics Laboratory, The Hospital for Sick Children Accession: SCV002587243.1 First in ClinVar: Oct 29, 2022 Last updated: Oct 29, 2022
Benign (Jul 15, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: no Allele origin: germline	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan Accession: SCV005087717.1 First in ClinVar: Jul 23, 2024 Last updated: Jul 23, 2024	Comment: This variant is classified as Benign based on local population frequency. This variant was detected in 41% of patients studied in a panel designed for … (more) This variant is classified as Benign based on local population frequency. This variant was detected in 41% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 38. Only high quality variants are reported. (less) Number of individuals with the variant: 38 Age: <18 years Sex: mixed
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005288609.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: unknown	Department of Pathology and Laboratory Medicine, Sinai Health System Additional submitter: Franklin by Genoox Study: The Canadian Open Genetics Repository (COGR) Accession: SCV001549515.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001932719.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001952503.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Benign (Feb 23, 2021)	no assertion criteria provided Method: clinical testing	NPHS2-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004800158.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Likely pathogenic (Jan 01, 2016)	Flagged submission flagged submission Method: clinical testing Reason: Outlier claim with insufficient supporting evidence Source: ClinGen	Nephrotic syndrome, type 2 Affected status: yes, no Allele origin: unknown	Human Genetics Disease in Children – Taif University, Taif University Accession: SCV000266492.1 First in ClinVar: Apr 14, 2016 Last updated: Apr 14, 2016	Observation 1: Observation 2:
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Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more

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.

Comment:

This variant is classified as Benign based on local population frequency. This variant was detected in 41% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 38. Only high quality variants are reported.

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 rs12406197 ...

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 Oct 13, 2024

ClinVar Genomic variation as it relates to human health

NM_014625.4(NPHS2):c.-51G>T

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs12406197 ...