11-2884860-GGGGGCCGGGGCCGGGGCC-GGGGGCCGGGGCC

Position:

• chr11-2884860-GGGGGCCGGGGCCGGGGCC-GGGGGCCGGGGCC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001122630.2(CDKN1C):​c.591_596delGGCCCC​(p.Ala198_Pro199del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,022,866 control chromosomes in the GnomAD database, including 22 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P197P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0064 (20 hom., cov: 32)
  • Exomes 𝑓: 0.00074 (2 hom.)
• Consequence: CDKN1C NM_001122630.2 disruptive_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.90

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-2884860-GGGGGCC-G is Benign according to our data. Variant chr11-2884860-GGGGGCC-G is described in ClinVar as [Likely_benign]. Clinvar id is 236967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-2884860-GGGGGCC-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00636 (912/143316) while in subpopulation AMR AF= 0.0411 (600/14612). AF 95% confidence interval is 0.0383. There are 20 homozygotes in gnomad4. There are 479 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 912 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN1C	NM_001122630.2	c.591_596delGGCCCC	p.Ala198_Pro199del	disruptive_inframe_deletion	2/4	ENST00000440480.8	NP_001116102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN1C	ENST00000440480.8	c.591_596delGGCCCC	p.Ala198_Pro199del	disruptive_inframe_deletion	2/4	1	NM_001122630.2	ENSP00000411257.2

Frequencies

GnomAD3 genomes AF: 0.00628 AC: 900 AN: 143222 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.00430

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0404

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000205

Gnomad SAS AF: 0.00306

Gnomad FIN AF: 0.000239

Gnomad MID AF: 0.00987

Gnomad NFE AF: 0.00158

Gnomad OTH AF: 0.00948

GnomAD4 exome AF: 0.000739 AC: 650 AN: 879550 Hom.: 2 AF XY: 0.000729 AC XY: 303 AN XY: 415590

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.0143

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00200

Gnomad4 FIN exome AF: 0.000162

Gnomad4 NFE exome AF: 0.000641

Gnomad4 OTH exome AF: 0.00106

GnomAD4 genome AF: 0.00636 AC: 912 AN: 143316 Hom.: 20 Cov.: 32 AF XY: 0.00686 AC XY: 479 AN XY: 69866

Gnomad4 AFR AF: 0.00437

Gnomad4 AMR AF: 0.0411

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000206

Gnomad4 SAS AF: 0.00284

Gnomad4 FIN AF: 0.000239

Gnomad4 NFE AF: 0.00158

Gnomad4 OTH AF: 0.00940

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 02, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	Jun 29, 2022	- -

Beckwith-Wiedemann syndrome Benign:2

Benign, criteria provided, single submitter	curation	Sema4, Sema4	Oct 20, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 08, 2017	- -

Beckwith-Wiedemann syndrome;C1846009:IMAGe syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 15, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

CDKN1C: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs759134767; hg19: chr11-2906090;