Variant 11-2884840-TCCGGGGCCGGGGCCGGGG-TCCGGGGCCGGGGCCGGGGCCGGGG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001122630.2(CDKN1C):c.611_616dupCCCCGG(p.Ala204_Pro205dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,129,312 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

CDKN1C
NM_001122630.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts P:1B:3

Conservation

PhyloP100: -0.198

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 -16 ACMG points.

BP6

Variant 11-2884840-T-TCCGGGG is Benign according to our data. Variant chr11-2884840-T-TCCGGGG is described in ClinVar as [Likely_benign]. Clinvar id is 192358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000244 (33/135222) while in subpopulation SAS AF= 0.00202 (8/3964). AF 95% confidence interval is 0.001. There are 0 homozygotes in gnomad4. There are 19 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2 link	c.611_616dupCCCCGG	p.Ala204_Pro205dup	conservative_inframe_insertion	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.611_616dupCCCCGG	p.Ala204_Pro205dup	conservative_inframe_insertion	Exon 2 of 4	1	NM_001122630.2	ENSP00000411257.2		P49918-2

Frequencies

GnomAD3 genomes

AF:

0.000244

AC:

AN:

135124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000110

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000722

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00202

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000317

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000418

AC:

AN:

23948

Hom.:

AF XY:

0.00

AC XY:

AN XY:

15782

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000860

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

101

AN:

994090

Hom.:

Cov.:

AF XY:

0.000116

AC XY:

AN XY:

475940

show subpopulations

Gnomad4 AFR exome

AF:

0.000104

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000225

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000678

Gnomad4 OTH exome

AF:

0.000137

GnomAD4 genome

AF:

0.000244

AC:

AN:

135222

Hom.:

Cov.:

AF XY:

0.000288

AC XY:

AN XY:

65872

show subpopulations

Gnomad4 AFR

AF:

0.000110

Gnomad4 AMR

AF:

0.0000722

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00202

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000317

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Pathogenic:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Beckwith-Wiedemann syndrome

Pathogenic:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 23, 2025	- -
Pathogenic, no assertion criteria provided	not provided	Centre de Recherche Saint Antoine, Université Pierre et Marie Curie	-	- -

CDKN1C-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 21, 2024

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). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

CDKN1C: BS1 -

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