11-2884958-GGACCGC-GGACCGCGACCGC

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP3BP6BS1BS2

The NM_001122630.2(CDKN1C):c.493_498dupGCGGTC(p.Val166_Leu167insAlaVal) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000513 in 1,051,706 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000054 ( 1 hom. )

Consequence

CDKN1C
NM_001122630.2 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.427

Publications

0 publications found

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 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

CDKN1C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001122630.2

BP6

Variant 11-2884958-G-GGACCGC is Benign according to our data. Variant chr11-2884958-G-GGACCGC is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 454009.

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000542 (49/904392) while in subpopulation SAS AF = 0.000116 (2/17192). AF 95% confidence interval is 0.0000431. There are 1 homozygotes in GnomAdExome4. There are 27 alleles in the male GnomAdExome4 subpopulation. Median coverage is 13. This position passed quality control check.

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2 link	c.493_498dupGCGGTC	p.Val166_Leu167insAlaVal	conservative_inframe_insertion	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.493_498dupGCGGTC	p.Val166_Leu167insAlaVal	conservative_inframe_insertion	Exon 2 of 4	1	NM_001122630.2	ENSP00000411257.2		P49918-2

Frequencies

GnomAD3 genomes

AF:

0.0000339

AC:

AN:

147314

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000605

Gnomad OTH

AF:

0.000491

GnomAD4 exome

AF:

0.0000542

AC:

AN:

904392

Hom.:

Cov.:

AF XY:

0.0000627

AC XY:

AN XY:

430524

show subpopulations

African (AFR)

AF:

0.0000550

AC:

AN:

18180

American (AMR)

AF:

0.00

AC:

AN:

6362

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10966

East Asian (EAS)

AF:

0.0000491

AC:

AN:

20378

South Asian (SAS)

AF:

0.000116

AC:

AN:

17192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

18936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2392

European-Non Finnish (NFE)

AF:

0.0000568

AC:

AN:

774438

Other (OTH)

AF:

0.0000281

AC:

AN:

35548

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000339

AC:

AN:

147314

Hom.:

Cov.:

AF XY:

0.0000279

AC XY:

AN XY:

71766

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40668

American (AMR)

AF:

0.00

AC:

AN:

14890

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3406

East Asian (EAS)

AF:

0.00

AC:

AN:

5084

South Asian (SAS)

AF:

0.00

AC:

AN:

4772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000605

AC:

AN:

66146

Other (OTH)

AF:

0.000491

AC:

AN:

2038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Beckwith-Wiedemann syndrome

Uncertain:1Benign:1

Jun 09, 2021

Sema4, Sema4

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Nov 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.43

Mutation Taster

=82/18

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over