Genetic Variant NM_001122630.2:c.591_596delGGCCCC (chr11-2884860-GGGGGCC-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001122630.2(CDKN1C):c.591_596delGGCCCC(p.Ala198_Pro199del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,022,866 control chromosomes in the GnomAD database, including 22 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P197P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0064 ( 20 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 2 hom. )

Consequence

CDKN1C
NM_001122630.2 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.90

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 11-2884860-GGGGGCC-G is Benign according to our data. Variant chr11-2884860-GGGGGCC-G is described in ClinVar as [Benign]. Clinvar id is 236967.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-2884860-GGGGGCC-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00636 (912/143316) while in subpopulation AMR AF= 0.0411 (600/14612). AF 95% confidence interval is 0.0383. There are 20 homozygotes in gnomad4. There are 479 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 912 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2 link	c.591_596delGGCCCC	p.Ala198_Pro199del	disruptive_inframe_deletion	Exon 2 of 4	ENST00000440480.8	NP_001116102.1	P49918-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKN1C	ENST00000440480.8 link	c.591_596delGGCCCC	p.Ala198_Pro199del	disruptive_inframe_deletion	Exon 2 of 4	1	NM_001122630.2	ENSP00000411257.2		P49918-2

Frequencies

GnomAD3 genomes

AF:

0.00628

AC:

900

AN:

143222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00430

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0404

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000205

Gnomad SAS

AF:

0.00306

Gnomad FIN

AF:

0.000239

Gnomad MID

AF:

0.00987

Gnomad NFE

AF:

0.00158

Gnomad OTH

AF:

0.00948

GnomAD4 exome

AF:

0.000739

AC:

650

AN:

879550

Hom.:

AF XY:

0.000729

AC XY:

303

AN XY:

415590

show subpopulations

Gnomad4 AFR exome

AF:

0.00111

Gnomad4 AMR exome

AF:

0.0143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00200

Gnomad4 FIN exome

AF:

0.000162

Gnomad4 NFE exome

AF:

0.000641

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00636

AC:

912

AN:

143316

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

479

AN XY:

69866

show subpopulations

Gnomad4 AFR

AF:

0.00437

Gnomad4 AMR

AF:

0.0411

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000206

Gnomad4 SAS

AF:

0.00284

Gnomad4 FIN

AF:

0.000239

Gnomad4 NFE

AF:

0.00158

Gnomad4 OTH

AF:

0.00940

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 02, 2018

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 29, 2022

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Beckwith-Wiedemann syndrome

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 20, 2020

Sema4, Sema4

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Beckwith-Wiedemann syndrome;C1846009:IMAGe syndrome

Benign:1

Aug 15, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CDKN1C: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over