NM_005559.4(LAMA1):c.184C>T (p.Arg62Ter) AND Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome - ClinVar

NM_005559.4(LAMA1):c.184C>T (p.Arg62Ter) AND Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Apr 10, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001647167.3

Allele description [Variation Report for NM_005559.4(LAMA1):c.184C>T (p.Arg62Ter)]

NM_005559.4(LAMA1):c.184C>T (p.Arg62Ter)

Gene:

LAMA1:laminin subunit alpha 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18p11.31

Genomic location:

Preferred name:

NM_005559.4(LAMA1):c.184C>T (p.Arg62Ter)

HGVS:

NC_000018.10:g.7080335G>A
NG_034251.1:g.42480C>T
NM_005559.4:c.184C>TMANE SELECT
NP_005550.2:p.Arg62Ter
NC_000018.9:g.7080334G>A

Protein change:

R62*

Links:

dbSNP: rs758223206

NCBI 1000 Genomes Browser:

rs758223206

Molecular consequence:

NM_005559.4:c.184C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome
Synonyms:: Poretti-Boltshauser syndrome
Identifiers:: MONDO: MONDO:0014419; MedGen: C4014821; Orphanet: 370022; OMIM: 615960

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001519155	Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 4, 2021)	inherited	research	PubMed (1) [See all records that cite this PMID]
SCV002499415	DASA	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 10, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001519155

Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 4, 2021)

inherited

research

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

SCV002499415

DASA

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 10, 2022)

germline

clinical testing

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	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	inherited	yes	not provided	not provided	not provided	not provided	not provided	research

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 Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris, SCV001519155.1

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

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

From DASA, SCV002499415.1

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

Description

The c.184C>T;p.(Arg62*) variant creates a premature translational stop signal in the LAMA1 gene. It is expected to result in an absent or disrupted protein product -PVS1. The variant is present at low allele frequencies population databases (rs758223206 – gnomAD 0.00007964%; ABraOM 0.000427 frequency - https://abraom.ib.usp.br/) - PM2_supporting. In summary, the currently available evidence indicates that the variant is likely pathogenic.

#	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		1	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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