Variant 11-2884917-GGCCGGAGCCGGAGCCGGA-GGCCGGAGCCGGA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_001122630.2(CDKN1C):c.534_539delTCCGGC(p.Pro179_Ala180del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000436 in 882,284 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 0 hom. )

Consequence

CDKN1C
NM_001122630.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 0.0360

Variant links:

Genes affected

CDKN1C (HGNC:1786): (cyclin dependent kinase inhibitor 1C) This gene is imprinted, with preferential expression of the maternal allele. The encoded protein is a tight-binding, strong inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations in this gene are implicated in sporadic cancers and Beckwith-Wiedemann syndorome, suggesting that this gene is a tumor suppressor candidate. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

CDKN1C links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 11-2884917-GGCCGGA-G is Benign according to our data. Variant chr11-2884917-GGCCGGA-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 236958.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1, Likely_benign=2}.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000723 (104/143898) while in subpopulation SAS AF= 0.00211 (10/4744). AF 95% confidence interval is 0.00147. There are 0 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 104 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2 link	c.534_539delTCCGGC	p.Pro179_Ala180del	disruptive_inframe_deletion	Exon 2 of 4	ENST00000440480.8	NP_001116102.1	P49918-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN1C	ENST00000440480.8 link	c.534_539delTCCGGC	p.Pro179_Ala180del	disruptive_inframe_deletion	Exon 2 of 4	1	NM_001122630.2	ENSP00000411257.2		P49918-2

Frequencies

GnomAD3 genomes

AF:

0.000723

AC:

104

AN:

143802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000957

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00204

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00179

Gnomad SAS

AF:

0.00211

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000275

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000381

AC:

281

AN:

738386

Hom.:

AF XY:

0.000390

AC XY:

136

AN XY:

348408

show subpopulations

Gnomad4 AFR exome

AF:

0.000783

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000523

Gnomad4 SAS exome

AF:

0.00130

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000353

Gnomad4 OTH exome

AF:

0.000569

GnomAD4 genome

AF:

0.000723

AC:

104

AN:

143898

Hom.:

Cov.:

AF XY:

0.000757

AC XY:

AN XY:

70026

show subpopulations

Gnomad4 AFR

AF:

0.000954

Gnomad4 AMR

AF:

0.00204

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00179

Gnomad4 SAS

AF:

0.00211

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000275

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	CDKN1C: BS1 -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 10, 2015	- -

CDKN1C-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 07, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Beckwith-Wiedemann syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 14, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over