VCV002721202.2 - ClinVar

NM_004448.4(ERBB2):c.3674_3679del (p.Gln1225_Asp1226del)

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.

(2)

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.

Conflicting classifications of pathogenicity
Uncertain significance(1); Likely benign(1)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_004448.4(ERBB2):c.3674_3679del (p.Gln1225_Asp1226del)

Variation ID: 2721202 Accession: VCV002721202.2

Type and length

Deletion, 6 bp

Location

Cytogenetic: 17q12 17: 39727945-39727950 (GRCh38) [ NCBI UCSC ] 17: 37884198-37884203 (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 14, 2024	Oct 8, 2024	Sep 20, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_004448.4:c.3674_3679del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_004439.2:p.Gln1225_Asp1226del	inframe deletion
NM_001005862.3:c.3584_3589del	NP_001005862.1:p.Gln1195_Asp1196del	inframe deletion
NM_001289936.2:c.3629_3634del	NP_001276865.1:p.Gln1210_Asp1211del	inframe deletion
NM_001289937.2:c.253_258del		3 prime UTR
NM_001382782.1:c.3584_3589del	NP_001369711.1:p.Gln1195_Asp1196del	inframe deletion
NM_001382783.1:c.3584_3589del	NP_001369712.1:p.Gln1195_Asp1196del	inframe deletion
NM_001382784.1:c.3791_3796del	NP_001369713.1:p.Gln1264_Asp1265del	inframe deletion
NM_001382785.1:c.3776_3781del	NP_001369714.1:p.Gln1259_Asp1260del	inframe deletion
NM_001382786.1:c.3755_3760del	NP_001369715.1:p.Gln1252_Asp1253del	inframe deletion
NM_001382787.1:c.3749_3754del	NP_001369716.1:p.Gln1250_Asp1251del	inframe deletion
NM_001382788.1:c.3704_3709del	NP_001369717.1:p.Gln1235_Asp1236del	inframe deletion
NM_001382789.1:c.3695_3700del	NP_001369718.1:p.Gln1232_Asp1233del	inframe deletion
NM_001382790.1:c.3671_3676del	NP_001369719.1:p.Gln1224_Asp1225del	inframe deletion
NM_001382791.1:c.3665_3670del	NP_001369720.1:p.Gln1222_Asp1223del	inframe deletion
NM_001382792.1:c.3638_3643del	NP_001369721.1:p.Gln1213_Asp1214del	inframe deletion
NM_001382793.1:c.3632_3637del	NP_001369722.1:p.Gln1211_Asp1212del	inframe deletion
NM_001382794.1:c.3632_3637del	NP_001369723.1:p.Gln1211_Asp1212del	inframe deletion
NM_001382795.1:c.3626_3631del	NP_001369724.1:p.Gln1209_Asp1210del	inframe deletion
NM_001382796.1:c.3587_3592del	NP_001369725.1:p.Gln1196_Asp1197del	inframe deletion
NM_001382797.1:c.3575_3580del	NP_001369726.1:p.Gln1192_Asp1193del	inframe deletion
NM_001382798.1:c.3518_3523del	NP_001369727.1:p.Gln1173_Asp1174del	inframe deletion
NM_001382799.1:c.3494_3499del	NP_001369728.1:p.Gln1165_Asp1166del	inframe deletion
NM_001382800.1:c.3488_3493del	NP_001369729.1:p.Gln1163_Asp1164del	inframe deletion
NM_001382801.1:c.3470_3475del	NP_001369730.1:p.Gln1157_Asp1158del	inframe deletion
NM_001382802.1:c.3416_3421del	NP_001369731.1:p.Gln1139_Asp1140del	inframe deletion
NM_001382803.1:c.253_258del		3 prime UTR
NM_001382804.1:c.2846_2851del	NP_001369733.1:p.Gln949_Asp950del	inframe deletion
NM_001382805.1:c.2723_2728del	NP_001369734.1:p.Gln908_Asp909del	inframe deletion
NM_001382806.1:c.2636_2641del	NP_001369735.1:p.Gln879_Asp880del	inframe deletion
NR_110535.2:n.3912_3917del		non-coding transcript variant
NC_000017.11:g.39727950_39727955del
NC_000017.10:g.37884203_37884208del
NG_007503.1:g.44811_44816del
LRG_724:g.44811_44816del
LRG_724t1:c.3584_3589del	LRG_724p1:p.Gln1195_Asp1196del
LRG_724t2:c.3674_3679del	LRG_724p2:p.Gln1225_Asp1226del
LRG_724t4:c.3629_3634del	LRG_724p4:p.Gln1210_Asp1211del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000017.11:39727944:GGACCAGGACC:GGACC

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.

Links

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.
Visceral neuropathy, familial, 2, autosomal recessive	Likely benign (1)	criteria provided, single submitter	Sep 20, 2024	RCV004723365.1
not provided	Uncertain significance (1)	criteria provided, single submitter	Jul 17, 2023	RCV003556380.2

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.
Uncertain significance (Jul 17, 2023)	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: SCV004275953.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024	Comment: This variant has not been reported in the literature in individuals affected with ERBB2-related conditions. This variant, c.3674_3679del, results in the deletion of 2 amino … (more) This variant has not been reported in the literature in individuals affected with ERBB2-related conditions. This variant, c.3674_3679del, results in the deletion of 2 amino acid(s) of the ERBB2 protein (p.Gln1225_Asp1226del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs755472707, gnomAD 0.004%). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. (less)
Likely benign (Sep 20, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Visceral neuropathy, familial, 2, autosomal recessive Affected status: no Allele origin: germline	3billion Accession: SCV005328990.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous … (more) The homozygous variant was found in patients diagnosed with another variant in a different gene, with no symptoms related to the gene containing the homozygous variant. (less)

Comment:

This variant has not been reported in the literature in individuals affected with ERBB2-related conditions. This variant, c.3674_3679del, results in the deletion of 2 amino acid(s) of the ERBB2 protein (p.Gln1225_Asp1226del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs755472707, gnomAD 0.004%). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.

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 this variant ...

Record last updated Oct 08, 2024

ClinVar Genomic variation as it relates to human health

NM_004448.4(ERBB2):c.3674_3679del (p.Gln1225_Asp1226del)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...