NM_016180.5(SLC45A2):c.593G>A (p.Gly198Asp) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 31, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV001757487.6

Allele description [Variation Report for NM_016180.5(SLC45A2):c.593G>A (p.Gly198Asp)]

NM_016180.5(SLC45A2):c.593G>A (p.Gly198Asp)

Gene:

SLC45A2:solute carrier family 45 member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5p13.2

Genomic location:

Preferred name:

NM_016180.5(SLC45A2):c.593G>A (p.Gly198Asp)

HGVS:

NC_000005.10:g.33963986C>T
NG_011691.2:g.25690G>A
NM_001012509.4:c.593G>A
NM_001297417.4:c.563-9482G>A
NM_016180.5:c.593G>AMANE SELECT
NP_001012527.2:p.Gly198Asp
NP_057264.4:p.Gly198Asp
NC_000005.9:g.33964091C>T
NM_016180.3:c.593G>A

Protein change:

G198D

Links:

dbSNP: rs201259497

NCBI 1000 Genomes Browser:

rs201259497

Molecular consequence:

NM_001297417.4:c.563-9482G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001012509.4:c.593G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_016180.5:c.593G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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uncharacterized protein LOC111445895 isoform X1 [Cucurbita moschata]
uncharacterized protein LOC111445895 isoform X1 [Cucurbita moschata]
gi|1279774951|ref|XP_022940195.1|

Protein
UI-H-BI4-aoe-e-10-0-UI.s1 NCI_CGAP_Sub8 Homo sapiens cDNA clone IMAGE:3084762 3'...
UI-H-BI4-aoe-e-10-0-UI.s1 NCI_CGAP_Sub8 Homo sapiens cDNA clone IMAGE:3084762 3', mRNA sequence
gi|11593742|gnl|dbEST|7037809|gb|BF 4.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002007678	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jan 3, 2023)	germline	clinical testing	Citation Link,
SCV002212594	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 31, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 18463683, 28976636, 29345414, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002007678

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jan 3, 2023)

germline

clinical testing

Citation Link,

SCV002212594

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 31, 2024)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Comprehensive analysis of oculocutaneous albinism among non-Hispanic caucasians shows that OCA1 is the most prevalent OCA type.

Hutton SM, Spritz RA.

J Invest Dermatol. 2008 Oct;128(10):2442-50. doi: 10.1038/jid.2008.109. Epub 2008 May 8.

PubMed [citation]

PMID:: 18463683
PMCID:: PMC3515683

Lessons of a day hospital: Comprehensive assessment of patients with albinism in a European setting.

Marti A, Lasseaux E, Ezzedine K, Léauté-Labrèze C, Boralevi F, Paya C, Coste V, Deroissart V, Arveiler B, Taieb A, Morice-Picard F.

Pigment Cell Melanoma Res. 2018 Mar;31(2):318-329. doi: 10.1111/pcmr.12651. Epub 2017 Oct 21.

PubMed [citation]

PMID:: 28976636

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV002007678.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 27019209, 34662886, 18463683, 28976636)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002212594.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 198 of the SLC45A2 protein (p.Gly198Asp). This variant is present in population databases (rs201259497, gnomAD 0.007%). This missense change has been observed in individual(s) with clinical features of oculocutaneous albinism (PMID: 18463683, 28976636, 29345414; Invitae). 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: 1316040). 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 SLC45A2 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

#	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

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