rs878853629

Variant names:

• chr11-2884935-AGCCGGGGCCGGGGCCGGG-A
• rs878853629
• NM_001122630.2:c.504_521delCCCGGCCCCGGCCCCGGC

Your query was ambiguous. Multiple possible variants found:

• chr11-2884935-AGCCGGGGCCGGGGCCGGG-A
• chr11-2884935-AGCCGGGGCCGGGGCCGGG-AGCCGGG
• chr11-2884935-AGCCGGGGCCGGGGCCGGG-AGCCGGGGCCGGG
• chr11-2884935-AGCCGGGGCCGGGGCCGGG-AGCCGGGGCCGGGGCCGGGGCCGGG
• chr11-2884935-AGCCGGGGCCGGGGCCGGG-AGCCGGGGCCGGGGCCGGGGCCGGGGCCGGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001122630.2(CDKN1C):​c.504_521delCCCGGCCCCGGCCCCGGC​(p.Pro169_Ala174del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 901,018 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: CDKN1C NM_001122630.2 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.666

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 -10 ACMG points.

• BP6: Variant 11-2884935-AGCCGGGGCCGGGGCCGGG-A is Benign according to our data. Variant chr11-2884935-AGCCGGGGCCGGGGCCGGG-A is described in ClinVar as [Likely_benign]. Clinvar id is 412854.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000236 (32/135466) while in subpopulation NFE AF= 0.000356 (22/61714). AF 95% confidence interval is 0.000241. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2	c.504_521delCCCGGCCCCGGCCCCGGC	p.Pro169_Ala174del	disruptive_inframe_deletion	Exon 2 of 4	ENST00000440480.8	NP_001116102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN1C	ENST00000440480.8	c.504_521delCCCGGCCCCGGCCCCGGC	p.Pro169_Ala174del	disruptive_inframe_deletion	Exon 2 of 4	1	NM_001122630.2	ENSP00000411257.2

Frequencies

GnomAD3 genomes AF: 0.000236 AC: 32 AN: 135376 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000539

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000286

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000516

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000356

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000320 AC: 245 AN: 765552 Hom.: 0 AF XY: 0.000325 AC XY: 118 AN XY: 362948

Gnomad4 AFR exome AF: 0.000137

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000687

Gnomad4 NFE exome AF: 0.000343

Gnomad4 OTH exome AF: 0.000174

GnomAD4 genome AF: 0.000236 AC: 32 AN: 135466 Hom.: 0 Cov.: 32 AF XY: 0.000213 AC XY: 14 AN XY: 65860

Gnomad4 AFR AF: 0.0000537

Gnomad4 AMR AF: 0.000286

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000516

Gnomad4 NFE AF: 0.000356

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000650 Hom.: 0

Bravo AF: 0.000204

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Beckwith-Wiedemann syndrome Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

CDKN1C-related disorder Benign:1

Apr 22, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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: rs878853629; hg19: chr11-2906165;