rs878853636

chr11-2884872-CGGGGCCGGGGCCGGGGCT-Cchr11-2884872-CGGGGCCGGGGCCGGGGCT-CGGGGCCGGGGCCGGGGCTGGGGCCGGGGCCGGGGCT

Variant summary

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

The NM_001122630.2(CDKN1C):c.567_584del(p.Ala200_Pro205del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 840,520 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P189P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00030 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00018 (0 hom.)
• Consequence: CDKN1C NM_001122630.2 inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.36

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 11-2884872-CGGGGCCGGGGCCGGGGCT-C is Benign according to our data. Variant chr11-2884872-CGGGGCCGGGGCCGGGGCT-C is described in ClinVar as [Likely_benign]. Clinvar id is 236962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN1C	NM_001122630.2	c.567_584del	p.Ala200_Pro205del	inframe_deletion	2/4	ENST00000440480.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN1C	ENST00000440480.8	c.567_584del	p.Ala200_Pro205del	inframe_deletion	2/4	1	NM_001122630.2	A2

Frequencies

GnomAD3 genomes AF: 0.000300 AC: 41 AN: 136442 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000523

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000713

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000841

Gnomad SAS AF: 0.00113

Gnomad FIN AF: 0.000248

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000533

GnomAD4 exome AF: 0.000178 AC: 125 AN: 703982 Hom.: 0 AF XY: 0.000166 AC XY: 55 AN XY: 330714

Gnomad4 AFR exome AF: 0.000882

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000793

Gnomad4 SAS exome AF: 0.000949

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000128

Gnomad4 OTH exome AF: 0.000372

GnomAD4 genome AF: 0.000300 AC: 41 AN: 136538 Hom.: 1 Cov.: 33 AF XY: 0.000240 AC XY: 16 AN XY: 66532

Gnomad4 AFR AF: 0.000521

Gnomad4 AMR AF: 0.0000712

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000843

Gnomad4 SAS AF: 0.00113

Gnomad4 FIN AF: 0.000248

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.000531

Alfa AF: 0.000169 Hom.: 0

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 10, 2021

- -

Beckwith-Wiedemann syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 16, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2023

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: rs878853636; hg19: chr11-2906102;