NM_001122630.2:c.596_597insGGCCCCGGCCCCGGCCCCGGCCCCGGCCCC

Variant names:

• chr11-2884860-G-GGGGGCCGGGGCCGGGGCCGGGGCCGGGGCC
• rs759134767
• NM_001122630.2:c.596_597insGGCCCCGGCCCCGGCCCCGGCCCCGGCCCC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001122630.2(CDKN1C):​c.596_597insGGCCCCGGCCCCGGCCCCGGCCCCGGCCCC​(p.Pro199_Ala200insAlaProAlaProAlaProAlaProAlaPro) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000698 in 143,230 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0000070 (0 hom., cov: 32)
• Consequence: CDKN1C NM_001122630.2 disruptive_inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.73

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 11-2884860-G-GGGGGCCGGGGCCGGGGCCGGGGCCGGGGCC is Benign according to our data. Variant chr11-2884860-G-GGGGGCCGGGGCCGGGGCCGGGGCCGGGGCC is described in ClinVar as [Likely_benign]. Clinvar id is 1528820.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.596_597insGGCCCCGGCCCCGGCCCCGGCCCCGGCCCC	p.Pro199_Ala200insAlaProAlaProAlaProAlaProAlaPro	disruptive_inframe_insertion	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.596_597insGGCCCCGGCCCCGGCCCCGGCCCCGGCCCC	p.Pro199_Ala200insAlaProAlaProAlaProAlaProAlaPro	disruptive_inframe_insertion	Exon 2 of 4	1	NM_001122630.2	ENSP00000411257.2

Frequencies

GnomAD3 genomes AF: 0.00000698 AC: 1 AN: 143230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000253

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 12

GnomAD4 genome AF: 0.00000698 AC: 1 AN: 143230 Hom.: 0 Cov.: 32 AF XY: 0.0000143 AC XY: 1 AN XY: 69764

Gnomad4 AFR AF: 0.0000253

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: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Beckwith-Wiedemann syndrome Benign:1

Jul 10, 2023

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs759134767; hg19: chr11-2906090;