rs1064792992

Variant names:

• chr11-2884960-ACCGCGACCGCGACCGGAG-A
• rs1064792992
• NM_001122630.2:c.479_496delCTCCGGTCGCGGTCGCGG

Your query was ambiguous. Multiple possible variants found:

• chr11-2884960-ACCGCGACCGCGACCGGAG-A
• chr11-2884960-ACCGCGACCGCGACCGGAG-ACCGCGACCGCGACCGGAGCCGCGACCGCGACCGGAG

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP3 BP6_Moderate

The NM_001122630.2(CDKN1C):​c.479_496delCTCCGGTCGCGGTCGCGG​(p.Ala160_Ala165del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000115 in 868,832 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A160A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: CDKN1C NM_001122630.2 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29
• Publications: 0 publications found

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]

CDKN1C Gene-Disease associations (from GenCC):

• Beckwith-Wiedemann syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• IMAGe syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Illumina, G2P, Ambry Genetics
• rhabdomyosarcoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• Beckwith-Wiedemann syndrome due to CDKN1C mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• intrauterine growth restriction-short stature-early adult-onset diabetes syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Silver-Russell syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001122630.2
• BP6: Variant 11-2884960-ACCGCGACCGCGACCGGAG-A is Benign according to our data. Variant chr11-2884960-ACCGCGACCGCGACCGGAG-A is described in ClinVar as Likely_benign. ClinVar VariationId is 412865.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2	c.479_496delCTCCGGTCGCGGTCGCGG	p.Ala160_Ala165del	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.479_496delCTCCGGTCGCGGTCGCGG	p.Ala160_Ala165del	disruptive_inframe_deletion	Exon 2 of 4	1	NM_001122630.2	ENSP00000411257.2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000115 AC: 1 AN: 868832 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 413936

African (AFR) AF: 0.00 AC: 0 AN: 17554

American (AMR) AF: 0.00 AC: 0 AN: 6370

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10820

East Asian (EAS) AF: 0.00 AC: 0 AN: 20434

South Asian (SAS) AF: 0.00 AC: 0 AN: 16502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19038

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2354

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 741410

Other (OTH) AF: 0.0000291 AC: 1 AN: 34350

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Beckwith-Wiedemann syndrome Benign:1

Jul 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=190/10	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1064792992; hg19: chr11-2906190;