NM_001384140.1(PCDH15):c.1863_1864dup (p.Ser622fs) AND Usher syndrome type 1F

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 24, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003062261.3

Allele description [Variation Report for NM_001384140.1(PCDH15):c.1863_1864dup (p.Ser622fs)]

NM_001384140.1(PCDH15):c.1863_1864dup (p.Ser622fs)

Gene:

PCDH15:protocadherin related 15 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

10q21.1

Genomic location:

Preferred name:

NM_001384140.1(PCDH15):c.1863_1864dup (p.Ser622fs)

Other names:

NM_001384140.1:c.1863_1864dup

HGVS:

NC_000010.11:g.54132928TA[3]
NG_009191.3:g.1501252TA[3]
NM_001142763.2:c.1878_1879dup
NM_001142764.2:c.1863_1864dup
NM_001142765.2:c.1784+20169TA[3]
NM_001142766.2:c.1863_1864dup
NM_001142767.2:c.1752_1753dup
NM_001142768.2:c.1797_1798dup
NM_001142769.3:c.1899_1900dup
NM_001142770.3:c.1863_1864dup
NM_001142771.2:c.1878_1879dup
NM_001142772.2:c.1863_1864dup
NM_001142773.2:c.1797_1798dup
NM_001354404.2:c.1797_1798dup
NM_001354411.2:c.1884_1885dup
NM_001354420.2:c.1863_1864dup
NM_001354429.2:c.1863_1864dup
NM_001354430.2:c.1863_1864dup
NM_001384140.1:c.1863_1864dupMANE SELECT
NM_033056.4:c.1863_1864dup
NP_001136235.1:p.Ser627fs
NP_001136236.1:p.Ser622fs
NP_001136238.1:p.Ser622fs
NP_001136239.1:p.Ser585fs
NP_001136240.1:p.Ser600fs
NP_001136241.1:p.Ser634fs
NP_001136242.1:p.Ser622fs
NP_001136243.1:p.Ser627fs
NP_001136244.1:p.Ser622fs
NP_001136245.1:p.Ser600fs
NP_001341333.1:p.Ser600fs
NP_001341340.1:p.Ser629fs
NP_001341349.1:p.Ser622fs
NP_001341358.1:p.Ser622fs
NP_001341359.1:p.Ser622fs
NP_001371069.1:p.Ser622fs
NP_149045.3:p.Ser622fs
NC_000010.10:g.55892687_55892688insTA
NC_000010.10:g.55892688TA[3]
NC_000010.11:g.54132930_54132931dup

Protein change:

S585fs

Molecular consequence:

NM_001142763.2:c.1878_1879dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001142764.2:c.1863_1864dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001142766.2:c.1863_1864dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001142767.2:c.1752_1753dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001142768.2:c.1797_1798dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001142769.3:c.1899_1900dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001142770.3:c.1863_1864dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001142771.2:c.1878_1879dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001142772.2:c.1863_1864dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001142773.2:c.1797_1798dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354404.2:c.1797_1798dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354411.2:c.1884_1885dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354420.2:c.1863_1864dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354429.2:c.1863_1864dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354430.2:c.1863_1864dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001384140.1:c.1863_1864dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_033056.4:c.1863_1864dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001142765.2:c.1784+20169TA[3] - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Usher syndrome type 1F (USH1F)
Synonyms:: USHER SYNDROME, TYPE IF
Identifiers:: MONDO: MONDO:0011186; MedGen: C1865885; Orphanet: 231169; Orphanet: 886; OMIM: 602083

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003761071	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 24, 2023)	germline	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003761071

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 24, 2023)

germline

curation

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV003761071.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

Description

The p.Ser622fs variant in PCDH15 has been reported in 3 individuals with Usher syndrome type 1F (PMID: 26166082, 30029497, 33724713) and has been identified in 0.005% (1/18338) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs764292129). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. Of the 3 affected individuals, 2 of those were homozygotes, which increases the likelihood that the p.Ser622fs variant is pathogenic (PMID: 26166082, 30029497). This variant is predicted to cause a frameshift, which alters the protein‚Äôs amino acid sequence beginning at position 622 and leads to a premature termination codon 9 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the PCDH15 gene is an established disease mechanism in autosomal recessive Usher syndrome type 1F. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Usher syndrome type 1F. ACMG/AMP Criteria applied: PVS1, PM2_supporting, PM3 (Richards 2015).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine