rs878853629

chr11-2884935-AGCCGGGGCCGGGGCCGGG-Achr11-2884935-AGCCGGGGCCGGGGCCGGG-AGCCGGGchr11-2884935-AGCCGGGGCCGGGGCCGGG-AGCCGGGGCCGGGchr11-2884935-AGCCGGGGCCGGGGCCGGG-AGCCGGGGCCGGGGCCGGGGCCGGGchr11-2884935-AGCCGGGGCCGGGGCCGGG-AGCCGGGGCCGGGGCCGGGGCCGGGGCCGGG

Variant summary

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

The NM_001122630.2(CDKN1C):c.504_521del(p.Ala178_Pro183del) variant causes a 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A168A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00024 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: CDKN1C NM_001122630.2 inframe_deletion
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts 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 -12 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_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN1C	NM_001122630.2	c.504_521del	p.Ala178_Pro183del	inframe_deletion	2/4	ENST00000440480.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN1C	ENST00000440480.8	c.504_521del	p.Ala178_Pro183del	inframe_deletion	2/4	1	NM_001122630.2	A2

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, multiple submitters, no conflicts

Submissions by phenotype

Beckwith-Wiedemann syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 23, 2023

- -

CDKN1C-related condition Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 22, 2023

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;