VCV000300167.6 - ClinVar

NM_033056.4(PCDH15):c.5653C>T (p.His1885Tyr)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Uncertain significance
Uncertain significance (2)

2 out of 2 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_033056.4(PCDH15):c.5653C>T (p.His1885Tyr)

Variation ID: 300167 Accession: VCV000300167.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10q21.1 10: 53822073 (GRCh38) [ NCBI UCSC ] 10: 55581833 (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	Dec 31, 2022	Sep 8, 2021

HGVS

Nucleotide	Protein	Molecular consequence
NM_001384140.1:c.4368-1843C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_033056.4:c.5653C>T MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_149045.3:p.His1885Tyr	missense
NM_001142763.2:c.5674C>T	NP_001136235.1:p.His1892Tyr	missense
NM_001142764.2:c.5659C>T	NP_001136236.1:p.His1887Tyr	missense
NM_001142765.2:c.5446C>T	NP_001136237.1:p.His1816Tyr	missense
NM_001142766.2:c.5644C>T	NP_001136238.1:p.His1882Tyr	missense
NM_001142767.2:c.5533C>T	NP_001136239.1:p.His1845Tyr	missense
NM_001142768.2:c.5593C>T	NP_001136240.1:p.His1865Tyr	missense
NM_001142769.3:c.4409+3063C>T		intron variant
NM_001142770.3:c.4373+3063C>T		intron variant
NM_001142771.2:c.4388+3063C>T		intron variant
NM_001142772.2:c.4373+3063C>T		intron variant
NM_001142773.2:c.5584C>T	NP_001136245.1:p.His1862Tyr	missense
NM_001354404.2:c.5587C>T	NP_001341333.1:p.His1863Tyr	missense
NM_001354411.2:c.4388+5320C>T		intron variant
NM_001354420.2:c.4367+5320C>T		intron variant
NM_001354429.2:c.4368-4060C>T		intron variant
NC_000010.11:g.53822073G>A
NC_000010.10:g.55581833G>A
NG_009191.3:g.1812110C>T

... more HGVS ... less HGVS

Protein change

H1885Y, H1862Y, H1865Y, H1882Y, H1863Y, H1892Y, H1845Y, H1816Y, H1887Y

Other names

Canonical SPDI

NC_000010.11:53822072:G:A

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), exomes 0.00000

Trans-Omics for Precision Medicine (TOPMed) 0.00001

Links

ClinGen: CA10631823 dbSNP: rs886047060 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.
PCDH15		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	3871	3973

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.
Usher syndrome type 1	Uncertain significance (1)	criteria provided, single submitter	Jan 13, 2018	RCV000311631.5
Autosomal recessive nonsyndromic hearing loss 23 Usher syndrome type 1D Usher syndrome type 1F	Uncertain significance (1)	criteria provided, single submitter	Sep 8, 2021	RCV002494938.1

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.	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.
Uncertain significance (Jan 13, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Usher syndrome type 1	Illumina Laboratory Services, Illumina Accession: SCV000363103.3 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

Uncertain significance (Sep 08, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Usher syndrome type 1D Usher syndrome type 1F Autosomal recessive nonsyndromic hearing loss 23	Fulgent Genetics, Fulgent Genetics Accession: SCV002779109.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

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.

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 rs886047060 ...

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 Apr 13, 2026