NM_198525.3(KIF7):c.2917C>T (p.Arg973Ter) AND Acrocallosal syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jun 19, 2018
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:: RCV000201660.8

Allele description [Variation Report for NM_198525.3(KIF7):c.2917C>T (p.Arg973Ter)]

NM_198525.3(KIF7):c.2917C>T (p.Arg973Ter)

Gene:

KIF7:kinesin family member 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q26.1

Genomic location:

Preferred name:

NM_198525.3(KIF7):c.2917C>T (p.Arg973Ter)

HGVS:

NC_000015.10:g.89631689G>A
NG_030338.1:g.28763C>T
NM_198525.3:c.2917C>TMANE SELECT
NP_940927.2:p.Arg973Ter
NC_000015.9:g.90174920G>A
NM_198525.2:c.2917C>T

Protein change:

R973*

Links:

dbSNP: rs202229910

NCBI 1000 Genomes Browser:

rs202229910

Molecular consequence:

NM_198525.3:c.2917C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Acrocallosal syndrome (ACLS)
Synonyms:: HALLUX DUPLICATION, POSTAXIAL POLYDACTYLY, AND ABSENCE OF CORPUS CALLOSUM; Acrocallosal syndrome, Schinzel type; Schinzel syndrome 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008708; MedGen: C0796147; Orphanet: 36; OMIM: 200990

Recent activity

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K-EST0144908 S14K402 Homo sapiens cDNA clone S14K402-59-H06 5', mRNA sequence
K-EST0144908 S14K402 Homo sapiens cDNA clone S14K402-59-H06 5', mRNA sequence
gi|19941156|gnl|dbEST|11986804|gb|B 87.1|

Nucleotide
Uterine cancer
Uterine cancer

MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000256438	UW Hindbrain Malformation Research Program, University of Washington See additional submitters University of Washington Center for Mendelian Genomics, University of Washington	criteria provided, single submitter (Bachmann-Gagescu et al. (J Med Genet. 2015))	Pathogenic (Feb 23, 2015)	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV000832019	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 19, 2018)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 19666503, 21552264, 21633164, 26648833, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000256438

UW Hindbrain Malformation Research Program, University of Washington

See additional submitters

criteria provided, single submitter

(Bachmann-Gagescu et al. (J Med Genet. 2015))

Pathogenic
(Feb 23, 2015)

unknown

research

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

SCV000832019

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 19, 2018)

germline

clinical testing

PubMed (5)
[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	unknown	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity.

Bachmann-Gagescu R, Dempsey JC, Phelps IG, O'Roak BJ, Knutzen DM, Rue TC, Ishak GE, Isabella CR, Gorden N, Adkins J, Boyle EA, de Lacy N, O'Day D, Alswaid A, Ramadevi A R, Lingappa L, Lourenço C, Martorell L, Garcia-Cazorla À, Ozyürek H, Haliloğlu G, Tuysuz B, et al.

J Med Genet. 2015 Aug;52(8):514-22. doi: 10.1136/jmedgenet-2015-103087. Epub 2015 Jun 19.

PubMed [citation]

PMID:: 26092869
PMCID:: PMC5082428

Mouse Kif7/Costal2 is a cilia-associated protein that regulates Sonic hedgehog signaling.

Liem KF Jr, He M, Ocbina PJ, Anderson KV.

Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13377-82. doi: 10.1073/pnas.0906944106. Epub 2009 Jul 29.

PubMed [citation]

PMID:: 19666503
PMCID:: PMC2726420

See all PubMed Citations (6)

Details of each submission

From UW Hindbrain Malformation Research Program, University of Washington, SCV000256438.1

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

From Invitae, SCV000832019.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in KIF7 are known to be pathogenic (PMID: 19666503, 21552264, 21633164, 26648833). This variant has been observed in an individual affected with Joubert syndrome (PMID:¬†26092869). ClinVar contains an entry for this variant (Variation ID: 217671). This variant is present in population databases (rs202229910, ExAC 0.1%). This sequence change creates a premature translational stop signal (p.Arg973*) in the KIF7 gene. It is expected to result in an absent or disrupted protein product.

#	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: Jun 23, 2024

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