rs515726203

Variant names:

• chr11-2884675-A-C
• rs515726203
• NM_001122630.2:c.782T>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001122630.2(CDKN1C):​c.782T>G​(p.Ile261Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CDKN1C NM_001122630.2 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 1.04

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2	c.782T>G	p.Ile261Ser	missense_variant	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.782T>G	p.Ile261Ser	missense_variant	Exon 2 of 4	1	NM_001122630.2	ENSP00000411257.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

IMAGe syndrome Other:1

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GeneReviews

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.54	.;T;T
M_CAP	Pathogenic	0.99	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Benign	0.34	N;N;.
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-2.1	N;N;N
REVEL	Uncertain	0.62
Sift	Uncertain	0.0020	D;D;D
Sift4G	Benign	0.16	T;T;T
Polyphen		0.86	P;P;.
Vest4		0.88
MutPred		0.23		Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);.;
MVP		0.86
MPC		1.8
ClinPred		0.32	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.46
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs515726203; hg19: chr11-2905905;