NM_001122630.2:c.*5+23_*5+24dupGG

Variant names:

• chr11-2883974-G-GCC
• rs34289096
• NM_001122630.2:c.*5+23_*5+24dupGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001122630.2(CDKN1C):​c.*5+23_*5+24dupGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0037 in 1,553,992 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0038 (10 hom.)
• Consequence: CDKN1C NM_001122630.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• Beckwith-Wiedemann syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• IMAGe syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Illumina, G2P, Ambry Genetics
• rhabdomyosarcoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• Beckwith-Wiedemann syndrome due to CDKN1C mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• intrauterine growth restriction-short stature-early adult-onset diabetes syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Silver-Russell syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 11-2883974-G-GCC is Benign according to our data. Variant chr11-2883974-G-GCC is described in ClinVar as [Likely_benign]. Clinvar id is 2641505.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00288 (437/151700) while in subpopulation AMR AF = 0.00484 (74/15278). AF 95% confidence interval is 0.00396. There are 0 homozygotes in GnomAd4. There are 221 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 437 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2	c.*5+23_*5+24dupGG		intron_variant	Intron 3 of 3	ENST00000440480.8	NP_001116102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN1C	ENST00000440480.8	c.*5+24_*5+25insGG		intron_variant	Intron 3 of 3	1	NM_001122630.2	ENSP00000411257.2

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 438 AN: 151584 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000992

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00492

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00562

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00355

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.00287 AC: 448 AN: 155866 AF XY: 0.00279

Gnomad AFR exome AF: 0.000650

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.00336

Gnomad EAS exome AF: 0.000695

Gnomad FIN exome AF: 0.00469

Gnomad NFE exome AF: 0.00358

Gnomad OTH exome AF: 0.00138

GnomAD4 exome AF: 0.00378 AC: 5306 AN: 1402292 Hom.: 10 Cov.: 32 AF XY: 0.00372 AC XY: 2578 AN XY: 692672

African (AFR) AF: 0.000868 AC: 28 AN: 32264

American (AMR) AF: 0.00348 AC: 130 AN: 37324

Ashkenazi Jewish (ASJ) AF: 0.00330 AC: 83 AN: 25184

East Asian (EAS) AF: 0.000494 AC: 18 AN: 36404

South Asian (SAS) AF: 0.00128 AC: 103 AN: 80194

European-Finnish (FIN) AF: 0.00472 AC: 217 AN: 46022

Middle Eastern (MID) AF: 0.00124 AC: 7 AN: 5654

European-Non Finnish (NFE) AF: 0.00423 AC: 4576 AN: 1081166

Other (OTH) AF: 0.00248 AC: 144 AN: 58080

GnomAD4 genome AF: 0.00288 AC: 437 AN: 151700 Hom.: 0 Cov.: 0 AF XY: 0.00298 AC XY: 221 AN XY: 74142

African (AFR) AF: 0.000989 AC: 41 AN: 41444

American (AMR) AF: 0.00484 AC: 74 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3462

East Asian (EAS) AF: 0.000393 AC: 2 AN: 5084

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4814

European-Finnish (FIN) AF: 0.00562 AC: 59 AN: 10500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00355 AC: 241 AN: 67812

Other (OTH) AF: 0.00285 AC: 6 AN: 2106

Alfa AF: 0.00169 Hom.: 952

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CDKN1C: BS1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs34289096; hg19: chr11-2905204;