NM_001378454.1(ALMS1):c.11960G>A (p.Trp3987Ter) AND Alstrom syndrome

Germline classification:: Pathogenic (1 submission)
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:: RCV002630828.3

Allele description [Variation Report for NM_001378454.1(ALMS1):c.11960G>A (p.Trp3987Ter)]

NM_001378454.1(ALMS1):c.11960G>A (p.Trp3987Ter)

Genes:

ALMS1:ALMS1 centrosome and basal body associated protein [Gene - OMIM - HGNC]
LOC126806252:BRD4-independent group 4 enhancer GRCh37_chr2:73828496-73829695 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

2p13.1

Genomic location:

Preferred name:

NM_001378454.1(ALMS1):c.11960G>A (p.Trp3987Ter)

HGVS:

NC_000002.12:g.73601282G>A
NG_011690.1:g.220530G>A
NG_082576.1:g.14G>A
NM_001378454.1:c.11960G>AMANE SELECT
NM_015120.4:c.11963G>A
NP_001365383.1:p.Trp3987Ter
NP_055935.3:p.Trp3988Ter
NP_055935.4:p.Trp3988Ter
LRG_741t1:c.11963G>A
LRG_741:g.220530G>A
LRG_741p1:p.Trp3988Ter
NC_000002.11:g.73828409G>A
NM_015120.3:c.11963G>A

Protein change:

W3987*

Molecular consequence:

NM_001378454.1:c.11960G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_015120.4:c.11963G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Alstrom syndrome (ALMS)
Synonyms:: Alstrom's syndrome
Identifiers:: MONDO: MONDO:0008763; MedGen: C0268425; Orphanet: 64; OMIM: 203800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002962895	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 17, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17594715, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002962895

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome.

Marshall JD, Hinman EG, Collin GB, Beck S, Cerqueira R, Maffei P, Milan G, Zhang W, Wilson DI, Hearn T, Tavares P, Vettor R, Veronese C, Martin M, So WV, Nishina PM, Naggert JK.

Hum Mutat. 2007 Nov;28(11):1114-23.

PubMed [citation]

PMID:: 17594715

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002962895.2

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

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp3988*) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715).

#	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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