NM_001305581.2(LRMDA):c.664C>T (p.Arg222Ter) AND not provided

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Sep 17, 2022
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:: RCV001699103.5

Allele description [Variation Report for NM_001305581.2(LRMDA):c.664C>T (p.Arg222Ter)]

NM_001305581.2(LRMDA):c.664C>T (p.Arg222Ter)

Gene:

LRMDA:leucine rich melanocyte differentiation associated [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q22.3

Genomic location:

Preferred name:

NM_001305581.2(LRMDA):c.664C>T (p.Arg222Ter)

HGVS:

NC_000010.11:g.76557271C>T
NG_042180.1:g.1130626C>T
NM_001305581.2:c.664C>TMANE SELECT
NM_032024.5:c.580C>T
NP_001292510.1:p.Arg222Ter
NP_114413.1:p.Arg194Ter
NC_000010.10:g.78317029C>T
NM_032024.3:c.580C>T
NP_114413.1:p.Arg194*
NR_131178.2:n.1018C>T

Protein change:

R194*; ARG194TER

Links:

OMIM: 614537.0001; dbSNP: rs587776952

NCBI 1000 Genomes Browser:

rs587776952

Molecular consequence:

NR_131178.2:n.1018C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001305581.2:c.664C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_032024.5:c.580C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001923802	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely pathogenic	germline	clinical testing
SCV001974961	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV003441529	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Sep 17, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23395477, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001923802

Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided

Likely pathogenic

germline

clinical testing

SCV001974961

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided

Pathogenic

germline

clinical testing

SCV003441529

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Sep 17, 2022)

germline

clinical testing

PubMed (2)
[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

Mutations in c10orf11, a melanocyte-differentiation gene, cause autosomal-recessive albinism.

Grønskov K, Dooley CM, Østergaard E, Kelsh RN, Hansen L, Levesque MP, Vilhelmsen K, Møllgård K, Stemple DL, Rosenberg T.

Am J Hum Genet. 2013 Mar 7;92(3):415-21. doi: 10.1016/j.ajhg.2013.01.006. Epub 2013 Feb 7.

PubMed [citation]

PMID:: 23395477
PMCID:: PMC3591853

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001923802.1

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

#	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 Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001974961.1

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

#	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 Invitae, SCV003441529.2

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this premature translational stop signal affects C10orf11 function (PMID: 23395477). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 41916). This premature translational stop signal has been observed in individual(s) with albinism (PMID: 23395477). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs587776952, gnomAD 0.02%). This sequence change creates a premature translational stop signal (p.Arg194*) in the C10orf11 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 5 amino acid(s) of the C10orf11 protein.

#	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: Feb 14, 2024

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