NM_145269.5(CIBAR1):c.478C>T (p.Arg160Ter) AND Polydactyly, postaxial, type A9

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 20, 2023
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:: RCV000723368.6

Allele description [Variation Report for NM_145269.5(CIBAR1):c.478C>T (p.Arg160Ter)]

NM_145269.5(CIBAR1):c.478C>T (p.Arg160Ter)

Gene:

CIBAR1:CBY1 interacting BAR domain containing 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q22.1

Genomic location:

Preferred name:

NM_145269.5(CIBAR1):c.478C>T (p.Arg160Ter)

Other names:

CIBAR1, ARG160TER (rs368652620)

HGVS:

NC_000008.11:g.93709810C>T
NM_001283034.2:c.478C>T
NM_145269.5:c.478C>TMANE SELECT
NP_001269963.1:p.Arg160Ter
NP_660312.2:p.Arg160Ter
NC_000008.10:g.94722038C>T
NM_001283034.1:c.478C>T
NR_104267.2:n.576C>T
NR_104268.2:n.576C>T
NR_156451.2:n.838C>T
NR_156452.2:n.760C>T
NR_156453.2:n.650C>T

Protein change:

R160*; ARG160TER

Links:

OMIM: 617273.0001; dbSNP: rs368652620

NCBI 1000 Genomes Browser:

rs368652620

Molecular consequence:

NR_104267.2:n.576C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104268.2:n.576C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_156451.2:n.838C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_156452.2:n.760C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_156453.2:n.650C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001283034.2:c.478C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_145269.5:c.478C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Polydactyly, postaxial, type A9
Identifiers:: MONDO: MONDO:0032603; MedGen: C4748721; OMIM: 618219

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000854768	OMIM	no assertion criteria provided	Pathogenic (Jul 12, 2024)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV003925609	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 20, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000854768

OMIM

no assertion criteria provided

Pathogenic
(Jul 12, 2024)

germline

literature only

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

SCV003925609

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 20, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

FAM92A Underlies Nonsyndromic Postaxial Polydactyly in Humans and an Abnormal Limb and Digit Skeletal Phenotype in Mice.

Schrauwen I, Giese AP, Aziz A, Lafont DT, Chakchouk I, Santos-Cortez RLP, Lee K, Acharya A, Khan FS, Ullah A, Nickerson DA, Bamshad MJ, Ali G, Riazuddin S, Ansar M, Ahmad W, Ahmed ZM, Leal SM.

J Bone Miner Res. 2019 Feb;34(2):375-386. doi: 10.1002/jbmr.3594. Epub 2018 Nov 5.

PubMed [citation]

PMID:: 30395363
PMCID:: PMC6489482

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

Details of each submission

From OMIM, SCV000854768.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 3 Pakistani brothers with postaxial polydactyly type A9 (PAPA9; 618219), Schrauwen et al. (2018) identified homozygosity for a c.478C-T transition (c.478C-T, NM_001283034.1) in the FAM92A gene, resulting in an arg160-to-ter (R160X) substitution within the BAR domain. Their unaffected parents and an unaffected brother were heterozygous for the mutation, which was not found in 186 in-house Pakistani control DNA samples or in the Greater Middle East Variome Project database. However, the variant was present at a low frequency in the gnomAD database (all populations MAF, 2.04 x 10(-5); South East Asians MAF, 6.55 x 10(-5)). Experiments in transfected COS-7 cells demonstrated that both FAM92A homodimerization and the FAM92A/Chibby1 (CBY; 607757) complex were disrupted with the mutant protein. In addition, recruitment and colocalization of FAM92A with Chybby1 at the base of cilia was impaired with the R160X mutant compared to wildtype FAM92A.

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

From Institute of Human Genetics, University of Leipzig Medical Center, SCV003925609.1

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

Description

This variant was identified as homozygous._x000D_ Criteria applied: PVS1, PM3, PM2_SUP

#	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

Last Updated: Jul 23, 2024

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