11-2884878-CGGGGCCGGGGCT-CGGGGCCGGGGCTGGGGCCGGGGCT

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_001122630.2(CDKN1C):c.578_579insAGCCCCGGCCCC(p.Ala202_Pro205dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000264 in 140,330 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P193P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000054 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDKN1C NM_001122630.2 inframe_insertion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.287

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 11-2884878-C-CGGGGCCGGGGCT is Benign according to our data. Variant chr11-2884878-C-CGGGGCCGGGGCT is described in ClinVar as [Likely_benign]. Clinvar id is 236961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 37 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN1C	NM_001122630.2	c.578_579insAGCCCCGGCCCC	p.Ala202_Pro205dup	inframe_insertion	2/4	ENST00000440480.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN1C	ENST00000440480.8	c.578_579insAGCCCCGGCCCC	p.Ala202_Pro205dup	inframe_insertion	2/4	1	NM_001122630.2	A2

Frequencies

GnomAD3 genomes AF: 0.000264 AC: 37 AN: 140226 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000762

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000306

Gnomad EAS AF: 0.00555

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000959

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000537 AC: 40 AN: 745382 Hom.: 0 Cov.: 11 AF XY: 0.0000713 AC XY: 25 AN XY: 350506

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00138

Gnomad4 SAS exome AF: 0.0000655

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000404

Gnomad4 OTH exome AF: 0.0000775

GnomAD4 genome AF: 0.000264 AC: 37 AN: 140330 Hom.: 0 Cov.: 33 AF XY: 0.000307 AC XY: 21 AN XY: 68430

Gnomad4 AFR AF: 0.0000760

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000306

Gnomad4 EAS AF: 0.00556

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000959

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Beckwith-Wiedemann syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Likely benign, criteria provided, single submitter	curation	Sema4, Sema4	Dec 16, 2020	- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

CDKN1C: BS1 -

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: rs878853634; hg19: chr11-2906108;