NM_052989.3(IFT122):c.3426_3430del (p.Ser1143fs) AND Cranioectodermal dysplasia 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 7, 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:: RCV001783467.5

Allele description [Variation Report for NM_052989.3(IFT122):c.3426_3430del (p.Ser1143fs)]

NM_052989.3(IFT122):c.3426_3430del (p.Ser1143fs)

Gene:

IFT122:intraflagellar transport 122 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3q22.1

Genomic location:

Preferred name:

NM_052989.3(IFT122):c.3426_3430del (p.Ser1143fs)

HGVS:

NC_000003.12:g.129519141_129519145del
NG_023392.1:g.84017_84021del
NM_001280541.2:c.3405_3409del
NM_001280545.2:c.2976_2980del
NM_001280546.2:c.2799_2803del
NM_018262.4:c.3249_3253del
NM_052985.4:c.3579_3583del
NM_052989.3:c.3426_3430delMANE SELECT
NM_052990.3:c.3096_3100del
NP_001267470.1:p.Ser1136fs
NP_001267474.1:p.Ser993fs
NP_001267475.1:p.Ser934fs
NP_060732.2:p.Ser1084fs
NP_443711.2:p.Ser1194fs
NP_443715.1:p.Ser1143fs
NP_443716.1:p.Ser1033fs
NC_000003.11:g.129237983_129237987del
NC_000003.11:g.129237984_129237988del
NM_052985.3:c.3579_3583del

Protein change:

S1033fs

Links:

dbSNP: rs1299632365

NCBI 1000 Genomes Browser:

rs1299632365

Molecular consequence:

NM_001280541.2:c.3405_3409del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001280545.2:c.2976_2980del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001280546.2:c.2799_2803del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_018262.4:c.3249_3253del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_052985.4:c.3579_3583del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_052989.3:c.3426_3430del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_052990.3:c.3096_3100del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cranioectodermal dysplasia 1 (CED1)
Synonyms:: LEVIN SYNDROME I; Levin syndrome 1
Identifiers:: MONDO: MONDO:0021093; MedGen: C0432235; Orphanet: 1515; OMIM: 218330

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002023129	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 13, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003255668	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 7, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20493458, 23826986, 26792575, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002023129

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 13, 2020)

germline

clinical testing

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

SCV003255668

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 7, 2022)

germline

clinical testing

PubMed (4)
[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

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

Cranioectodermal Dysplasia, Sensenbrenner syndrome, is a ciliopathy caused by mutations in the IFT122 gene.

Walczak-Sztulpa J, Eggenschwiler J, Osborn D, Brown DA, Emma F, Klingenberg C, Hennekam RC, Torre G, Garshasbi M, Tzschach A, Szczepanska M, Krawczynski M, Zachwieja J, Zwolinska D, Beales PL, Ropers HH, Latos-Bielenska A, Kuss AW.

Am J Hum Genet. 2010 Jun 11;86(6):949-56. doi: 10.1016/j.ajhg.2010.04.012. Epub 2010 May 20.

PubMed [citation]

PMID:: 20493458
PMCID:: PMC3032067

See all PubMed Citations (5)

Details of each submission

From Revvity Omics, Revvity, SCV002023129.3

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

From Invitae, SCV003255668.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Ser1194Argfs*3) in the IFT122 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IFT122 are known to be pathogenic (PMID: 20493458, 23826986, 26792575). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with IFT122-related conditions. ClinVar contains an entry for this variant (Variation ID: 1323103). 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: Mar 16, 2024

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