VCV000397626.4 - ClinVar

NM_004667.6(HERC2):c.12757G>A (p.Ala4253Thr)

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.

(3)

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.

Uncertain significance

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004667.6(HERC2):c.12757G>A (p.Ala4253Thr)

Variation ID: 397626 Accession: VCV000397626.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 15q13.1 15: 28130208 (GRCh38) [ NCBI UCSC ] 15: 28375354 (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	Mar 27, 2017	Oct 7, 2023	May 15, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_004667.6:c.12757G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_004658.3:p.Ala4253Thr	missense
NC_000015.10:g.28130208C>T
NC_000015.9:g.28375354C>T
NG_016355.1:g.196942G>A

Protein change

A4253T

Other names

Canonical SPDI

NC_000015.10:28130207: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.

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

Trans-Omics for Precision Medicine (TOPMed) 0.00011

Exome Aggregation Consortium (ExAC) 0.00012

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015

The Genome Aggregation Database (gnomAD) 0.00024

Links

ClinGen: CA7440220 dbSNP: rs145535698 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.
HERC2		-	-	GRCh38 GRCh38 GRCh38 GRCh37	839	1152

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.
Global developmental delay	Uncertain significance (1)	criteria provided, single submitter	Feb 21, 2017	RCV000449631.1
Developmental delay with autism spectrum disorder and gait instability	Uncertain significance (1)	criteria provided, single submitter	May 15, 2023	RCV003333069.1
not provided	Uncertain significance (1)	criteria provided, single submitter	Jan 20, 2023	RCV002525533.1

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.
Uncertain significance (Feb 21, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	None Affected status: yes Allele origin: germline	Claritas Genomics Accession: SCV000537847.1 First in ClinVar: Mar 27, 2017 Last updated: Mar 27, 2017	Sex: female
Uncertain significance (Jan 20, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV003194943.1 First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023	Comment: In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Uncertain significance (May 15, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Developmental delay with autism spectrum disorder and gait instability Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004040755.1 First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023

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.

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 rs145535698 ...

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 08, 2024

ClinVar Genomic variation as it relates to human health

NM_004667.6(HERC2):c.12757G>A (p.Ala4253Thr)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs145535698 ...