NM_001122630.2(CDKN1C):c.425_442dup (p.Val142_Pro147dup) AND Beckwith-Wiedemann syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 27, 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:: RCV001052754.5

Allele description [Variation Report for NM_001122630.2(CDKN1C):c.425_442dup (p.Val142_Pro147dup)]

NM_001122630.2(CDKN1C):c.425_442dup (p.Val142_Pro147dup)

Gene:

CDKN1C:cyclin dependent kinase inhibitor 1C [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

11p15.4

Genomic location:

Preferred name:

NM_001122630.2(CDKN1C):c.425_442dup (p.Val142_Pro147dup)

HGVS:

NC_000011.10:g.2885020_2885037dup
NG_008022.1:g.5734_5751dup
NM_000076.2:c.458_475dup
NM_001122630.2:c.425_442dupMANE SELECT
NM_001122631.2:c.425_442dup
NM_001362474.2:c.458_475dup
NM_001362475.2:c.255+170_255+187dup
NP_000067.1:p.Val153_Pro158dup
NP_001116102.1:p.Val142_Pro147dup
NP_001116103.1:p.Val142_Pro147dup
NP_001349403.1:p.Val153_Pro158dup
LRG_533t1:c.458_475dup
LRG_533:g.5734_5751dup
LRG_533p1:p.Val153_Pro158dup
NC_000011.9:g.2906244_2906245insCCGGGGCTGGAGCCAGGA
NC_000011.9:g.2906250_2906267dup

Links:

dbSNP: rs1443296311

NCBI 1000 Genomes Browser:

rs1443296311

Molecular consequence:

NM_000076.2:c.458_475dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001122630.2:c.425_442dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001122631.2:c.425_442dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001362474.2:c.458_475dup - inframe_insertion - [Sequence Ontology: SO:0001821]
NM_001362475.2:c.255+170_255+187dup - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Beckwith-Wiedemann syndrome (BWS)
Synonyms:: Exomphalos macroglossia gigantism syndrome; EMG Syndrome
Identifiers:: MONDO: MONDO:0007534; MedGen: C0004903; Orphanet: 116; OMIM: 130650

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001216979	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 27, 2023)	germline	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

SCV001216979

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 27, 2023)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001216979.5

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

Description

This variant, c.458_475dup, results in the insertion of 6 amino acid(s) of the CDKN1C protein (p.Val153_Pro158dup), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CDKN1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 848902). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. RNA analysis performed to evaluate the impact of this variant on mRNA splicing indicates it does not significantly alter splicing (Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 20, 2024

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