NM_001384140.1(PCDH15):c.841A>G (p.Thr281Ala) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 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:: RCV001844739.3

Allele description [Variation Report for NM_001384140.1(PCDH15):c.841A>G (p.Thr281Ala)]

NM_001384140.1(PCDH15):c.841A>G (p.Thr281Ala)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

10q21.1

Genomic location:

Preferred name:

NM_001384140.1(PCDH15):c.841A>G (p.Thr281Ala)

Other names:

NM_001384140.1(PCDH15):c.841A>G; p.Thr281Ala

HGVS:

NC_000010.11:g.54317306T>C
NG_009191.3:g.1316877A>G
NM_001142763.2:c.856A>G
NM_001142764.2:c.841A>G
NM_001142765.2:c.841A>G
NM_001142766.2:c.841A>G
NM_001142767.2:c.730A>G
NM_001142768.2:c.775A>G
NM_001142769.3:c.856A>G
NM_001142770.3:c.841A>G
NM_001142771.2:c.856A>G
NM_001142772.2:c.841A>G
NM_001142773.2:c.775A>G
NM_001354404.2:c.775A>G
NM_001354411.2:c.841A>G
NM_001354420.2:c.841A>G
NM_001354429.2:c.841A>G
NM_001354430.2:c.841A>G
NM_001384140.1:c.841A>GMANE SELECT
NM_033056.4:c.841A>G
NP_001136235.1:p.Thr286Ala
NP_001136236.1:p.Thr281Ala
NP_001136237.1:p.Thr281Ala
NP_001136238.1:p.Thr281Ala
NP_001136239.1:p.Thr244Ala
NP_001136240.1:p.Thr259Ala
NP_001136241.1:p.Thr286Ala
NP_001136242.1:p.Thr281Ala
NP_001136243.1:p.Thr286Ala
NP_001136244.1:p.Thr281Ala
NP_001136245.1:p.Thr259Ala
NP_001341333.1:p.Thr259Ala
NP_001341340.1:p.Thr281Ala
NP_001341349.1:p.Thr281Ala
NP_001341358.1:p.Thr281Ala
NP_001341359.1:p.Thr281Ala
NP_001371069.1:p.Thr281Ala
NP_149045.3:p.Thr281Ala
NC_000010.10:g.56077066T>C
NM_033056.3:c.841A>G

Protein change:

T244A

Links:

dbSNP: rs773843633

NCBI 1000 Genomes Browser:

rs773843633

Molecular consequence:

NM_001142763.2:c.856A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001142764.2:c.841A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001142765.2:c.841A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001142766.2:c.841A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001142767.2:c.730A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001142768.2:c.775A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001142769.3:c.856A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001142770.3:c.841A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001142771.2:c.856A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001142772.2:c.841A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001142773.2:c.775A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354404.2:c.775A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354411.2:c.841A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354420.2:c.841A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354429.2:c.841A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354430.2:c.841A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001384140.1:c.841A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_033056.4:c.841A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002104028	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Aug 28, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27058588, 33090715 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002104028

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Aug 28, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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	clinical testing

Citations

PubMed

Investigation of Rare Single-Nucleotide PCDH15 Variants in Schizophrenia and Autism Spectrum Disorders.

Ishizuka K, Kimura H, Wang C, Xing J, Kushima I, Arioka Y, Oya-Ito T, Uno Y, Okada T, Mori D, Aleksic B, Ozaki N.

PLoS One. 2016;11(4):e0153224. doi: 10.1371/journal.pone.0153224.

PubMed [citation]

PMID:: 27058588
PMCID:: PMC4825995

Molecular diagnosis based on comprehensive genetic testing in 800 Chinese families with non-syndromic inherited retinal dystrophies.

Liu X, Tao T, Zhao L, Li G, Yang L.

Clin Exp Ophthalmol. 2021 Jan;49(1):46-59. doi: 10.1111/ceo.13875. Epub 2020 Nov 2.

PubMed [citation]

PMID:: 33090715

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002104028.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: PCDH15 c.841A>G (p.Thr281Ala) results in a non-conservative amino acid change located in the Cadherin-like domain (IPR002126) of the encoded protein sequence. Two of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251280 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.841A>G has been reported in the literature in individuals affected with autism spectrum disorders and retinitis pigmentosa (Ishizuka_2016, Liu_2020). These reports do not provide unequivocal conclusions about association of the variant with Usher Syndrome Type 1F. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 27058588, 33090715). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: Mar 30, 2024

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