VCV001428662.6 - ClinVar

NM_004448.4(ERBB2):c.3611C>G (p.Ala1204Gly)

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.

(1)

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, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004448.4(ERBB2):c.3611C>G (p.Ala1204Gly)

Variation ID: 1428662 Accession: VCV001428662.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q12 17: 39727887 (GRCh38) [ NCBI UCSC ] 17: 37884140 (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 28, 2022	Feb 20, 2024	Mar 27, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_004448.4:c.3611C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_004439.2:p.Ala1204Gly	missense
NM_001005862.3:c.3521C>G	NP_001005862.1:p.Ala1174Gly	missense
NM_001289936.2:c.3566C>G	NP_001276865.1:p.Ala1189Gly	missense
NM_001289937.2:c.*190C>G		3 prime UTR
NM_001382782.1:c.3521C>G	NP_001369711.1:p.Ala1174Gly	missense
NM_001382783.1:c.3521C>G	NP_001369712.1:p.Ala1174Gly	missense
NM_001382784.1:c.3728C>G	NP_001369713.1:p.Ala1243Gly	missense
NM_001382785.1:c.3713C>G	NP_001369714.1:p.Ala1238Gly	missense
NM_001382786.1:c.3692C>G	NP_001369715.1:p.Ala1231Gly	missense
NM_001382787.1:c.3686C>G	NP_001369716.1:p.Ala1229Gly	missense
NM_001382788.1:c.3641C>G	NP_001369717.1:p.Ala1214Gly	missense
NM_001382789.1:c.3632C>G	NP_001369718.1:p.Ala1211Gly	missense
NM_001382790.1:c.3608C>G	NP_001369719.1:p.Ala1203Gly	missense
NM_001382791.1:c.3602C>G	NP_001369720.1:p.Ala1201Gly	missense
NM_001382792.1:c.3575C>G	NP_001369721.1:p.Ala1192Gly	missense
NM_001382793.1:c.3569C>G	NP_001369722.1:p.Ala1190Gly	missense
NM_001382794.1:c.3569C>G	NP_001369723.1:p.Ala1190Gly	missense
NM_001382795.1:c.3563C>G	NP_001369724.1:p.Ala1188Gly	missense
NM_001382796.1:c.3524C>G	NP_001369725.1:p.Ala1175Gly	missense
NM_001382797.1:c.3512C>G	NP_001369726.1:p.Ala1171Gly	missense
NM_001382798.1:c.3455C>G	NP_001369727.1:p.Ala1152Gly	missense
NM_001382799.1:c.3431C>G	NP_001369728.1:p.Ala1144Gly	missense
NM_001382800.1:c.3425C>G	NP_001369729.1:p.Ala1142Gly	missense
NM_001382801.1:c.3407C>G	NP_001369730.1:p.Ala1136Gly	missense
NM_001382802.1:c.3353C>G	NP_001369731.1:p.Ala1118Gly	missense
NM_001382803.1:c.*190C>G		3 prime UTR
NM_001382804.1:c.2783C>G	NP_001369733.1:p.Ala928Gly	missense
NM_001382805.1:c.2660C>G	NP_001369734.1:p.Ala887Gly	missense
NM_001382806.1:c.2573C>G	NP_001369735.1:p.Ala858Gly	missense
NR_110535.2:n.3849C>G		non-coding transcript variant
NC_000017.11:g.39727887C>G
NC_000017.10:g.37884140C>G
NG_007503.1:g.44748C>G
LRG_724:g.44748C>G

... more HGVS ... less HGVS

Protein change

A1136G, A1144G, A1171G, A1201G, A1188G, A1189G, A1204G, A1229G, A1231G, A1238G, A1243G, A1174G, A1175G, A1190G, A1192G, A858G, A887G, A928G, A1118G, A1142G, A1152G, A1203G, A1211G, A1214G

Other names

Canonical SPDI

NC_000017.11:39727886:C:G

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.

The Genome Aggregation Database (gnomAD) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00001

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

Links

dbSNP: rs373605104 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.
ERBB2		-	-	GRCh38 GRCh37	679	694

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	Uncertain significance (1)	criteria provided, single submitter	Mar 27, 2021	RCV001948329.6

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 (Mar 27, 2021)	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: SCV002206648.3 First in ClinVar: Mar 28, 2022 Last updated: Feb 20, 2024	Comment: This variant is not present in population databases (ExAC no frequency). In summary, the available evidence is currently insufficient to determine the role of this … (more) This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ERBB2-related conditions. This sequence change replaces alanine with glycine at codon 1204 of the ERBB2 protein (p.Ala1204Gly). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and glycine. (less)

Comment:

This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with ERBB2-related conditions. This sequence change replaces alanine with glycine at codon 1204 of the ERBB2 protein (p.Ala1204Gly). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and glycine.

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 rs373605104 ...

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_004448.4(ERBB2):c.3611C>G (p.Ala1204Gly)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs373605104 ...