This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 489 of the OCA2 protein (p.Asn489Asp). This variant is present in population databases (rs121918170, gnomAD 0.07%). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 12876664, 18463683, 29345414). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 961). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt OCA2 protein function with a positive predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on OCA2 function (PMID: 25513726). For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_000275.3(OCA2):c.1465A>G (p.Asn489Asp)
Germline
Classification
Help
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.
(19)
Help
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.
Pathogenic/Likely pathogenic
19
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000275.3(OCA2):c.1465A>G (p.Asn489Asp)
Variation ID: 961 Accession: VCV000000961.64
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 15q13.1 15: 27983383 (GRCh38) [ NCBI UCSC ] 15: 28228529 (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 Oct 14, 2016 Oct 20, 2024 Sep 12, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000275.3:c.1465A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000266.2:p.Asn489Asp missense NM_001300984.2:c.1393A>G NP_001287913.1:p.Asn465Asp missense NC_000015.10:g.27983383T>C NC_000015.9:g.28228529T>C NG_009846.1:g.120930A>G Q04671:p.Asn489Asp - Protein change
- N489D, N465D
- Other names
- -
- Canonical SPDI
- NC_000015.10:27983382:T:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe 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.
-
Exome Aggregation Consortium (ExAC) 0.00031
The Genome Aggregation Database (gnomAD), exomes 0.00035
The Genome Aggregation Database (gnomAD) 0.00043
Trans-Omics for Precision Medicine (TOPMed) 0.00045
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| OCA2 | - | - |
GRCh38 GRCh38 GRCh38 GRCh37 |
1314 | 1623 | |
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. |
|---|---|---|---|---|
| Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Nov 7, 2021 | RCV000001012.20 | |
| Pathogenic/Likely pathogenic (9) |
criteria provided, multiple submitters, no conflicts
|
Sep 12, 2024 | RCV000413429.47 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Oct 31, 2018 | RCV000762940.4 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Mar 26, 2024 | RCV003466774.2 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Dec 12, 2023 | RCV003492280.1 | |
|
OCA2-related disorder
|
Pathogenic (1) |
no assertion criteria provided
|
Aug 20, 2024 | RCV003421891.6 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Oct 14, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Albinism, oculocutaneous, type II
Affected status: yes
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000596144.1
First in ClinVar: Oct 14, 2016 Last updated: Oct 14, 2016 |
|
|
|
Pathogenic
(Jun 23, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000226011.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
|
|
|
Pathogenic
(Oct 31, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Tyrosinase-positive oculocutaneous albinism
SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV000893363.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
|
|
|
Likely pathogenic
(Jul 27, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002020182.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(Jan 21, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001584382.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 489 of the OCA2 protein … (more)
This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 489 of the OCA2 protein (p.Asn489Asp). This variant is present in population databases (rs121918170, gnomAD 0.07%). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 12876664, 18463683, 29345414). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 961). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt OCA2 protein function with a positive predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on OCA2 function (PMID: 25513726). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Mar 26, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
SKIN/HAIR/EYE PIGMENTATION 1, BLUE/NONBLUE EYES
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004208966.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(Oct 19, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Tyrosinase-positive oculocutaneous albinism
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000914660.1
First in ClinVar: May 27, 2019 Last updated: May 27, 2019 |
Comment:
The TCN2 c.497_498delTC (p.Leu166ProfsTer7) variant results in a frameshift, and is predicted to result in premature termination of the protein. The p.Leu166ProfsTer7 variant has been … (more)
The TCN2 c.497_498delTC (p.Leu166ProfsTer7) variant results in a frameshift, and is predicted to result in premature termination of the protein. The p.Leu166ProfsTer7 variant has been reported in two studies and is found in a total of four unrelated probands with transcobalamin II deficiency including three in a homozygous state and one in a compound heterozygous state (Schiff et al. 2010; Trakadis et al. 2014). Control data are unavailable for this variant, which is reported at a frequency of 0.00048 in the African population of the Exome Aggregation Consortium. Based on the evidence and the potential impact of frameshift variants, the p.Leu166ProfsTer7 variant is classified as pathogenic for transcobalamin II deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
|
|
|
Pathogenic
(Nov 07, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Tyrosinase-positive oculocutaneous albinism
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV002040586.1
First in ClinVar: Dec 25, 2021 Last updated: Dec 25, 2021 |
|
|
|
Pathogenic
(Dec 12, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Oculocutaneous albinism
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004240913.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
Comment:
Variant summary: OCA2 c.1465A>G (p.Asn489Asp) results in a conservative amino acid change located in the Citrate transporter-like domain (IPR004680) of the encoded protein sequence. Four … (more)
Variant summary: OCA2 c.1465A>G (p.Asn489Asp) results in a conservative amino acid change located in the Citrate transporter-like domain (IPR004680) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00035 in 251496 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in OCA2 causing Oculocutaneous Albinism (0.00035 vs 0.0043), allowing no conclusion about variant significance. c.1465A>G has been reported in the literature in multiple individuals affected with Oculocutaneous Albinism (example: Lasseaux_2018). These data indicate that the variant is very likely to be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 29345414). Eleven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
|
Pathogenic
(Sep 12, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000490675.7
First in ClinVar: Jan 09, 2017 Last updated: Sep 29, 2024 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 13680365, … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 13680365, 30665703, 31233279, 9259203, 19060277, 23824587, 23345203, 25513726, 20801516, 12876664, 18326704, 18463683, 24118800, 21541274, 29345414, 28667292, 30414346, 31206972, 31980526, 31589614, 34361043, 38219857, 34758253, 34662886) (less)
|
|
|
Pathogenic
(Jan 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001250100.26
First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024 |
Comment:
OCA2: PM3:Very Strong, PM2, PP3, PP4
Number of individuals with the variant: 5
|
|
|
Pathogenic
(Sep 01, 2003)
|
no assertion criteria provided
Method: literature only
|
ALBINISM, OCULOCUTANEOUS, TYPE II
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000021162.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 14, 2016 |
Comment on evidence:
For discussion of the asn489-to-asp (N489D) mutation in the OCA2 gene that was found in compound heterozygous state in a patient with oculocutaneous albinism type … (more)
For discussion of the asn489-to-asp (N489D) mutation in the OCA2 gene that was found in compound heterozygous state in a patient with oculocutaneous albinism type II (OCA2; 203200) by King et al. (2003), see 611409.0009. (less)
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001741823.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
|
|
|
Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001958831.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001973382.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
|
|
|
Pathogenic
(Oct 30, 2023)
|
no assertion criteria provided
Method: clinical testing
|
Tyrosinase-positive oculocutaneous albinism
Affected status: yes
Allele origin:
germline
|
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas
Accession: SCV004099433.1
First in ClinVar: Nov 04, 2023 Last updated: Nov 04, 2023 |
|
|
|
Pathogenic
(Aug 20, 2024)
|
no assertion criteria provided
Method: clinical testing
|
OCA2-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004118645.3
First in ClinVar: Nov 20, 2023 Last updated: Oct 08, 2024 |
Comment:
The OCA2 c.1465A>G variant is predicted to result in the amino acid substitution p.Asn489Asp. This variant has been reported to be causative for autosomal recessive … (more)
The OCA2 c.1465A>G variant is predicted to result in the amino acid substitution p.Asn489Asp. This variant has been reported to be causative for autosomal recessive oculocutaneous albinism (Spritz et al. 1997. PubMed ID: 9259203; King et al. 2003. PubMed ID: 13680365; King et al. 2003. PubMed ID: 12876664; Hutton and Spritz. 2008. PubMed ID: 18326704). This variant is reported in 0.067% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant has been reported to be one of three recurrent pathogenic variants in the OCA2 gene and accounts for one of the alleles in ~7% of OCAII cases (Hutton and Spritz. 2008. PubMed ID: 18463683). Given the evidence, we interpret this variant as pathogenic. (less)
|
|
|
Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Tyrosinase-positive oculocutaneous albinism
Affected status: yes
Allele origin:
germline
|
Genomics England Pilot Project, Genomics England
Accession: SCV001760340.1
First in ClinVar: Jul 27, 2021 Last updated: Jul 27, 2021 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001921089.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Comment:
Comment:
The TCN2 c.497_498delTC (p.Leu166ProfsTer7) variant results in a frameshift, and is predicted to result in premature termination of the protein. The p.Leu166ProfsTer7 variant has been reported in two studies and is found in a total of four unrelated probands with transcobalamin II deficiency including three in a homozygous state and one in a compound heterozygous state (Schiff et al. 2010; Trakadis et al. 2014). Control data are unavailable for this variant, which is reported at a frequency of 0.00048 in the African population of the Exome Aggregation Consortium. Based on the evidence and the potential impact of frameshift variants, the p.Leu166ProfsTer7 variant is classified as pathogenic for transcobalamin II deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Comment:
Variant summary: OCA2 c.1465A>G (p.Asn489Asp) results in a conservative amino acid change located in the Citrate transporter-like domain (IPR004680) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00035 in 251496 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in OCA2 causing Oculocutaneous Albinism (0.00035 vs 0.0043), allowing no conclusion about variant significance. c.1465A>G has been reported in the literature in multiple individuals affected with Oculocutaneous Albinism (example: Lasseaux_2018). These data indicate that the variant is very likely to be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 29345414). Eleven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 13680365, 30665703, 31233279, 9259203, 19060277, 23824587, 23345203, 25513726, 20801516, 12876664, 18326704, 18463683, 24118800, 21541274, 29345414, 28667292, 30414346, 31206972, 31980526, 31589614, 34361043, 38219857, 34758253, 34662886)
Comment:
OCA2: PM3:Very Strong, PM2, PP3, PP4
Comment:
The OCA2 c.1465A>G variant is predicted to result in the amino acid substitution p.Asn489Asp. This variant has been reported to be causative for autosomal recessive oculocutaneous albinism (Spritz et al. 1997. PubMed ID: 9259203; King et al. 2003. PubMed ID: 13680365; King et al. 2003. PubMed ID: 12876664; Hutton and Spritz. 2008. PubMed ID: 18326704). This variant is reported in 0.067% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant has been reported to be one of three recurrent pathogenic variants in the OCA2 gene and accounts for one of the alleles in ~7% of OCAII cases (Hutton and Spritz. 2008. PubMed ID: 18463683). Given the evidence, we interpret this variant as 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:
This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 489 of the OCA2 protein (p.Asn489Asp). This variant is present in population databases (rs121918170, gnomAD 0.07%). This missense change has been observed in individual(s) with oculocutaneous albinism (PMID: 12876664, 18463683, 29345414). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 961). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt OCA2 protein function with a positive predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on OCA2 function (PMID: 25513726). For these reasons, this variant has been classified as Pathogenic.
Comment:
The TCN2 c.497_498delTC (p.Leu166ProfsTer7) variant results in a frameshift, and is predicted to result in premature termination of the protein. The p.Leu166ProfsTer7 variant has been reported in two studies and is found in a total of four unrelated probands with transcobalamin II deficiency including three in a homozygous state and one in a compound heterozygous state (Schiff et al. 2010; Trakadis et al. 2014). Control data are unavailable for this variant, which is reported at a frequency of 0.00048 in the African population of the Exome Aggregation Consortium. Based on the evidence and the potential impact of frameshift variants, the p.Leu166ProfsTer7 variant is classified as pathogenic for transcobalamin II deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Comment:
Variant summary: OCA2 c.1465A>G (p.Asn489Asp) results in a conservative amino acid change located in the Citrate transporter-like domain (IPR004680) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00035 in 251496 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in OCA2 causing Oculocutaneous Albinism (0.00035 vs 0.0043), allowing no conclusion about variant significance. c.1465A>G has been reported in the literature in multiple individuals affected with Oculocutaneous Albinism (example: Lasseaux_2018). These data indicate that the variant is very likely to be associated with disease. The following publication has been ascertained in the context of this evaluation (PMID: 29345414). Eleven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 13680365, 30665703, 31233279, 9259203, 19060277, 23824587, 23345203, 25513726, 20801516, 12876664, 18326704, 18463683, 24118800, 21541274, 29345414, 28667292, 30414346, 31206972, 31980526, 31589614, 34361043, 38219857, 34758253, 34662886)
Comment:
OCA2: PM3:Very Strong, PM2, PP3, PP4
Comment:
The OCA2 c.1465A>G variant is predicted to result in the amino acid substitution p.Asn489Asp. This variant has been reported to be causative for autosomal recessive oculocutaneous albinism (Spritz et al. 1997. PubMed ID: 9259203; King et al. 2003. PubMed ID: 13680365; King et al. 2003. PubMed ID: 12876664; Hutton and Spritz. 2008. PubMed ID: 18326704). This variant is reported in 0.067% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant has been reported to be one of three recurrent pathogenic variants in the OCA2 gene and accounts for one of the alleles in ~7% of OCAII cases (Hutton and Spritz. 2008. PubMed ID: 18463683). Given the evidence, we interpret this variant as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Molecular characterization of a series of 990 index patients with albinism. | Lasseaux E | Pigment cell & melanoma research | 2018 | PMID: 29345414 |
| An intracellular anion channel critical for pigmentation. | Bellono NW | eLife | 2014 | PMID: 25513726 |
| Relationship between foveal cone specialization and pit morphology in albinism. | Wilk MA | Investigative ophthalmology & visual science | 2014 | PMID: 24845642 |
| Birth prevalence and mutation spectrum in danish patients with autosomal recessive albinism. | Grønskov K | Investigative ophthalmology & visual science | 2009 | PMID: 19060277 |
| Comprehensive analysis of oculocutaneous albinism among non-Hispanic caucasians shows that OCA1 is the most prevalent OCA type. | Hutton SM | The Journal of investigative dermatology | 2008 | PMID: 18463683 |
| A comprehensive genetic study of autosomal recessive ocular albinism in Caucasian patients. | Hutton SM | Investigative ophthalmology & visual science | 2008 | PMID: 18326704 |
| MC1R mutations modify the classic phenotype of oculocutaneous albinism type 2 (OCA2). | King RA | American journal of human genetics | 2003 | PMID: 12876664 |
| Novel mutations of the P gene in type II oculocutaneous albinism (OCA2). | Spritz RA | Human mutation | 1997 | PMID: 9259203 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=OCA2 | - | - | - | - |
Text-mined citations for rs121918170 ...
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Record last updated Oct 20, 2024
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