Genetic Variant CDKN1C:p.Pro171_Ala174del (chr11-2884935-AGCCGGGGCCGGG-A) – ACMG Classification: Benign (-16 pts)

Variant summary

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

The NM_001122630.2(CDKN1C):c.510_521delCCCGGCCCCGGC(p.Pro171_Ala174del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 900,988 control chromosomes in the GnomAD database, including 8 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 7 hom. )

Consequence

CDKN1C
NM_001122630.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.666

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 11-2884935-AGCCGGGGCCGGG-A is Benign according to our data. Variant chr11-2884935-AGCCGGGGCCGGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 236955.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-2884935-AGCCGGGGCCGGG-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00123 (167/135464) while in subpopulation NFE AF= 0.00219 (135/61712). AF 95% confidence interval is 0.00189. There are 1 homozygotes in gnomad4. There are 69 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 167 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2 link	c.510_521delCCCGGCCCCGGC	p.Pro171_Ala174del	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.510_521delCCCGGCCCCGGC	p.Pro171_Ala174del	disruptive_inframe_deletion	Exon 2 of 4	1	NM_001122630.2	ENSP00000411257.2		P49918-2

Frequencies

GnomAD3 genomes

AF:

0.00123

AC:

167

AN:

135374

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000728

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000215

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000221

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000129

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00202

AC:

1545

AN:

765524

Hom.:

AF XY:

0.00199

AC XY:

724

AN XY:

362936

show subpopulations

Gnomad4 AFR exome

AF:

0.000752

Gnomad4 AMR exome

AF:

0.000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000138

Gnomad4 FIN exome

AF:

0.000153

Gnomad4 NFE exome

AF:

0.00224

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.00123

AC:

167

AN:

135464

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

65858

show subpopulations

Gnomad4 AFR

AF:

0.000725

Gnomad4 AMR

AF:

0.000214

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000221

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000129

Gnomad4 NFE

AF:

0.00219

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Beckwith-Wiedemann syndrome

Benign:2

Aug 26, 2020

Sema4, Sema4

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Jun 17, 2021

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Jan 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CDKN1C: BS1, BS2 -

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.

11-2884935-AGCCGGGGCCGGGGCCGGG-AGCCGGG

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