VCV000241450.49 - ClinVar

NM_023036.6(DNAI2):c.1574C>T (p.Ala525Val)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance (2); Likely benign (4)

6 out of 7 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_023036.6(DNAI2):c.1574C>T (p.Ala525Val)

Variation ID: 241450 Accession: VCV000241450.49

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q25.1 17: 74312082 (GRCh38) [ NCBI UCSC ] 17: 72308221 (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	Dec 6, 2016	Jun 20, 2026	Jan 19, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_023036.6:c.1574C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_075462.3:p.Ala525Val	missense
NM_001172810.3:c.1538C>T	NP_001166281.1:p.Ala513Val	missense
NM_001353167.2:c.1574C>T	NP_001340096.1:p.Ala525Val	missense
NC_000017.11:g.74312082C>T
NC_000017.10:g.72308221C>T
NG_016865.1:g.42836C>T

... more HGVS ... less HGVS

Protein change

A525V, A513V

Other names

Canonical SPDI

NC_000017.11:74312081:C:T

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.

0.00140 (T)

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

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015

The Genome Aggregation Database (gnomAD) 0.00036

The Genome Aggregation Database (gnomAD), exomes 0.00039

The Genome Aggregation Database (gnomAD) 0.00047

Trans-Omics for Precision Medicine (TOPMed) 0.00073

The Genome Aggregation Database (gnomAD), exomes 0.00076

Exome Aggregation Consortium (ExAC) 0.00082

1000 Genomes Project 30x 0.00109

1000 Genomes Project 0.00140

Links

ClinGen: CA8745833 dbSNP: rs145602856 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.
DNAI2		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	941	964

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	Conflicting classifications of pathogenicity (3)	criteria provided, conflicting classifications	Jan 19, 2026	RCV000232038.21
not specified	Likely benign (1)	criteria provided, single submitter	Jun 7, 2016	RCV000613204.5
Primary ciliary dyskinesia 9	Conflicting classifications of pathogenicity (2)	criteria provided, conflicting classifications	May 18, 2021	RCV001094498.10
not provided	Likely benign (1)	criteria provided, single submitter	Oct 1, 2023	RCV003417837.22

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.	Expand all rows Collapse all rows 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 benign (Jun 07, 2016) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	not specified	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000711308.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Comment: show The p.Ala525Val in exon 12 of DNAI2: This variant is not expected to have clinic al significance because it has been identified in 0.9% (74/8618) of East Asian c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs145602856) and due to a lack of conservation in mammals. Of note, six mammals have a valine (V) at this position despite high nearby amino acid co nservation. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: not provided more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: not provided Number of individuals with the variant: 1

Uncertain significance (Jan 12, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Primary ciliary dyskinesia 9	Illumina Laboratory Services, Illumina Accession: SCV000406370.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (May 18, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Primary ciliary dyskinesia 9	Pars Genome Lab Accession: SCV001736795.2 First in ClinVar: Jun 19, 2021 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no Sex: mixed

Likely benign (Oct 01, 2023) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV004144144.22 First in ClinVar: Nov 20, 2023 Last updated: Jun 20, 2026	Comment: show DNAI2: BP4 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Uncertain significance (Apr 08, 2015) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Primary ciliary dyskinesia	Ambry Genetics Accession: SCV002703584.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: show The p.A525V variant (also known as c.1574C>T), located in coding exon 11 of the DNAI2 gene, results from a C to T substitution at nucleotide position 1574. The alanine at codon 525 is replaced by valine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs145602856. Based on data from the 1000 Genomes Project, the T allele has an overall frequency of approximately 0.14% (3/2098) total alleles studied. The highest observed frequency was 0.59% (1/170) CEPH alleles. Based on data from the NHLBI Exome Sequencing Project (ESP), the T allele has an overall frequency of approximately 0.02% (2/13006) total alleles studied, having been observed in 0.02% (1/4406) African American alleles and 0.01% (1/8600) European American alleles. This amino acid position is poorly conserved on species alignment. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence for this variant is limited at this time, the clinical significance of this variant remains unclear. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Jan 19, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Primary ciliary dyskinesia	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000290684.10 First in ClinVar: Jul 01, 2016 Last updated: Feb 15, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Jan 29, 2020) N Not contributing to aggregate classification	no assertion criteria provided	Primary ciliary dyskinesia	Natera, Inc. Accession: SCV002088876.1 First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

The p.Ala525Val in exon 12 of DNAI2: This variant is not expected to have clinic al significance because it has been identified in 0.9% (74/8618) of East Asian c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs145602856) and due to a lack of conservation in mammals. Of note, six mammals have a valine (V) at this position despite high nearby amino acid co nservation.

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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

Comment:

The p.A525V variant (also known as c.1574C>T), located in coding exon 11 of the DNAI2 gene, results from a C to T substitution at nucleotide position 1574. The alanine at codon 525 is replaced by valine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs145602856. Based on data from the 1000 Genomes Project, the T allele has an overall frequency of approximately 0.14% (3/2098) total alleles studied. The highest observed frequency was 0.59% (1/170) CEPH alleles. Based on data from the NHLBI Exome Sequencing Project (ESP), the T allele has an overall frequency of approximately 0.02% (2/13006) total alleles studied, having been observed in 0.02% (1/4406) African American alleles and 0.01% (1/8600) European American alleles. This amino acid position is poorly conserved on species alignment. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence for this variant is limited at this time, the clinical significance of this variant remains unclear.

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 rs145602856 ...

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 Jul 15, 2026