NM_001378454.1(ALMS1):c.2221dup (p.Thr741fs) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 3, 2021
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:
RCV002424572.2

Allele description [Variation Report for NM_001378454.1(ALMS1):c.2221dup (p.Thr741fs)]

NM_001378454.1(ALMS1):c.2221dup (p.Thr741fs)

Gene:
ALMS1:ALMS1 centrosome and basal body associated protein [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
2p13.1
Genomic location:
Preferred name:
NM_001378454.1(ALMS1):c.2221dup (p.Thr741fs)
HGVS:
  • NC_000002.12:g.73448748dup
  • NG_011690.1:g.67996dup
  • NM_001378454.1:c.2221dupMANE SELECT
  • NM_015120.4:c.2224dup
  • NP_001365383.1:p.Thr741fs
  • NP_055935.4:p.Thr742fs
  • LRG_741t1:c.2224dup
  • LRG_741:g.67996dup
  • LRG_741p1:p.Thr742fs
  • NC_000002.11:g.73675874_73675875insA
  • NC_000002.11:g.73675875dup
  • NM_015120.4:c.2224dupA
Protein change:
T741fs
Links:
dbSNP: rs769291842
NCBI 1000 Genomes Browser:
rs769291842
Molecular consequence:
  • NM_001378454.1:c.2221dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_015120.4:c.2224dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002730210Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Nov 3, 2021) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Diffuse left ventricular interstitial fibrosis is associated with sub-clinical myocardial dysfunction in Alström Syndrome: an observational study.

Edwards NC, Moody WE, Yuan M, Warfield AT, Cramb R, Paisey RB, Geberhiwot T, Steeds RP.

Orphanet J Rare Dis. 2015 Jun 24;10:83. doi: 10.1186/s13023-015-0292-z.

PubMed [citation]
PMID:
26104972
PMCID:
PMC4483224

Monogenic diabetes syndromes: Locus-specific databases for Alström, Wolfram, and Thiamine-responsive megaloblastic anemia.

Astuti D, Sabir A, Fulton P, Zatyka M, Williams D, Hardy C, Milan G, Favaretto F, Yu-Wai-Man P, Rohayem J, López de Heredia M, Hershey T, Tranebjaerg L, Chen JH, Chaussenot A, Nunes V, Marshall B, McAfferty S, Tillmann V, Maffei P, Paquis-Flucklinger V, Geberhiwot T, et al.

Hum Mutat. 2017 Jul;38(7):764-777. doi: 10.1002/humu.23233. Epub 2017 Jun 1.

PubMed [citation]
PMID:
28432734
PMCID:
PMC5535005

Details of each submission

From Ambry Genetics, SCV002730210.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The c.2224dupA variant, located in coding exon 8 of the ALMS1 gene, results from a duplication of A at nucleotide position 2224, causing a translational frameshift with a predicted alternate stop codon (p.T742Nfs*2). This variant (also referred to as c.2218dupA) has been reported to co-occur with nonsense variants in the ALMS1 gene in individuals reported to have Alstrom syndrome (Edwards NC et al. Orphanet J Rare Dis, 2015 Jun;10:83; Astuti D et al. Hum Mutat, 2017 07;38:764-777). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024