rs778468310

Positions:

• chr11-2884840-TCCGGGGCCGGGGCCGGGGCGGGGG-T
• chr11-2884840-TCCGGGGCCGGGGCCGGGGCGGGGG-TCCGGGGCCGGGGCCGGGGCGGGGGCCGGGGCCGGGGCCGGGGCGGGGG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001122630.2(CDKN1C):​c.593_616del​(p.Ala198_Pro205del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000585 in 1,129,160 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000030 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: CDKN1C NM_001122630.2 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.949

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 11-2884840-TCCGGGGCCGGGGCCGGGGCGGGGG-T is Benign according to our data. Variant chr11-2884840-TCCGGGGCCGGGGCCGGGGCGGGGG-T is described in ClinVar as [Benign]. Clinvar id is 454020.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 62 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN1C	NM_001122630.2	c.593_616del	p.Ala198_Pro205del	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.593_616del	p.Ala198_Pro205del	inframe_deletion	2/4	1	NM_001122630.2	ENSP00000411257	A2

Frequencies

GnomAD3 genomes AF: 0.0000296 AC: 4 AN: 135120 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000826

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000159

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000624 AC: 62 AN: 994040 Hom.: 0 AF XY: 0.0000651 AC XY: 31 AN XY: 475914

Gnomad4 AFR exome AF: 0.0000518

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000112

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000139

Gnomad4 NFE exome AF: 0.0000655

Gnomad4 OTH exome AF: 0.0000274

GnomAD4 genome AF: 0.0000296 AC: 4 AN: 135120 Hom.: 0 Cov.: 33 AF XY: 0.0000152 AC XY: 1 AN XY: 65772

Gnomad4 AFR AF: 0.0000826

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000159

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Beckwith-Wiedemann syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 01, 2023

- -

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: rs778468310; hg19: chr11-2906070;