NM_001378454.1(ALMS1):c.4249del (p.Arg1417fs) AND Alstrom syndrome

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 15, 2023
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:: RCV000666481.3

Allele description [Variation Report for NM_001378454.1(ALMS1):c.4249del (p.Arg1417fs)]

NM_001378454.1(ALMS1):c.4249del (p.Arg1417fs)

Gene:

ALMS1:ALMS1 centrosome and basal body associated protein [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2p13.1

Genomic location:

Preferred name:

NM_001378454.1(ALMS1):c.4249del (p.Arg1417fs)

HGVS:

NC_000002.12:g.73450776del
NG_011690.1:g.70024del
NM_001378454.1:c.4249delMANE SELECT
NM_015120.4:c.4252del
NP_001365383.1:p.Arg1417fs
NP_055935.4:p.Arg1418fs
LRG_741t1:c.4252del
LRG_741:g.70024del
LRG_741p1:p.Arg1418fs
NC_000002.11:g.73677902del
NC_000002.11:g.73677903del
NM_001378454.1:c.4249del
NM_015120.4:c.4252delC

Protein change:

R1417fs

Links:

dbSNP: rs1553403851

NCBI 1000 Genomes Browser:

rs1553403851

Molecular consequence:

NM_001378454.1:c.4249del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_015120.4:c.4252del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000790784	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Apr 25, 2017)	unknown	clinical testing	Citation Link,
SCV002792795	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 26, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004540319	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 15, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17594715, 29588463, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000790784

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Apr 25, 2017)

unknown

clinical testing

Citation Link,

SCV002792795

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 26, 2022)

unknown

clinical testing

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

SCV004540319

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 15, 2023)

germline

clinical testing

PubMed (3)
[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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

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

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

See all PubMed Citations (4)

Details of each submission

From Counsyl, SCV000790784.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002792795.1

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

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

From Invitae, SCV004540319.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Arg1418Glyfs*55) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Alstr√∂m syndrome (PMID: 29588463). ClinVar contains an entry for this variant (Variation ID: 551424). 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: Feb 28, 2024

ClinVar

Relating variation to medicine