VCV002500231.1 - ClinVar

NM_001277115.2(DNAH11):c.13523_13524insCTGGAGTGGCTCTGCTTCTAG (p.Ala4508_Gly4509insTrpSerGlySerAlaSerSer)

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.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001277115.2(DNAH11):c.13523_13524insCTGGAGTGGCTCTGCTTCTAG (p.Ala4508_Gly4509insTrpSerGlySerAlaSerSer)

Variation ID: 2500231 Accession: VCV002500231.1

Type and length

Insertion, 21 bp

Location

Cytogenetic: 7p15.3 7: 21901226-21901227 (GRCh38) [ NCBI UCSC ] 7: 21940844-21940845 (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	May 7, 2023	May 6, 2023	Mar 30, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_001277115.2:c.13523_13524insCTGGAGTGGCTCTGCTTCTAG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001264044.1:p.Ala4508_Gly4509insTrpSerGlySerAlaSerSer	inframe insertion
NM_018719.5:c.1095_1096insCTAGAAGCAGAGCCACTCCAG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		3 prime UTR
NM_001127370.3:c.1095_1096insCTAGAAGCAGAGCCACTCCAG		3 prime UTR
NM_001127371.3:c.1095_1096insCTAGAAGCAGAGCCACTCCAG		3 prime UTR
NC_000007.14:g.21901226_21901227insCTGGAGTGGCTCTGCTTCTAG
NC_000007.13:g.21940844_21940845insCTGGAGTGGCTCTGCTTCTAG
NG_012886.2:g.363012_363013insCTGGAGTGGCTCTGCTTCTAG

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000007.14:21901226::CTGGAGTGGCTCTGCTTCTAG

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.
CDCA7L		-	-	GRCh38 GRCh37	30	208
DNAH11		-	-	GRCh38 GRCh37	5400	5782

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.
Primary ciliary dyskinesia 7	Likely pathogenic (1)	criteria provided, single submitter	Mar 30, 2021	RCV003224850.1

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.
Likely pathogenic (Mar 30, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Primary ciliary dyskinesia 7 Affected status: unknown Allele origin: germline	Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago Accession: SCV003920879.1 First in ClinVar: May 06, 2023 Last updated: May 06, 2023	Comment: DNAH11 NM_001277115.1 exon 82 p.Ala4508_Leu4514dup (c.13523_13543dup): This variant has been reported in the literature in at least 1 individual with abdominal abnormalities (Retterer 2016 PMID:26633542); … (more) DNAH11 NM_001277115.1 exon 82 p.Ala4508_Leu4514dup (c.13523_13543dup): This variant has been reported in the literature in at least 1 individual with abdominal abnormalities (Retterer 2016 PMID:26633542); however, it is highly likely that this individual represents a patient at our institution who carries a clinical diagnosis of primary ciliary dyskinesia and a likely disease causing variant in trans. This variant is not present in large control databases. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is a duplication of 21 nucleotides at position 13523 which results in an inframe duplication of 7 amino acids; this variant is not predicted to alter the reading frame, however the effect of this variant on the protein is unclear. In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant is classified as likely pathogenic. (less)

Comment:

DNAH11 NM_001277115.1 exon 82 p.Ala4508_Leu4514dup (c.13523_13543dup): This variant has been reported in the literature in at least 1 individual with abdominal abnormalities (Retterer 2016 PMID:26633542); however, it is highly likely that this individual represents a patient at our institution who carries a clinical diagnosis of primary ciliary dyskinesia and a likely disease causing variant in trans. This variant is not present in large control databases. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is a duplication of 21 nucleotides at position 13523 which results in an inframe duplication of 7 amino acids; this variant is not predicted to alter the reading frame, however the effect of this variant on the protein is unclear. In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant is classified as likely pathogenic.

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 Sep 01, 2024

ClinVar Genomic variation as it relates to human health

NM_001277115.2(DNAH11):c.13523_13524insCTGGAGTGGCTCTGCTTCTAG (p.Ala4508_Gly4509insTrpSerGlySerAlaSerSer)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...