rs1060500179

Variant names:

• chr11-2885272-C-A
• NM_001122630.2:c.185G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-2885272-C-A
• chr11-2885272-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001122630.2(CDKN1C):​c.185G>T​(p.Gly62Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000014 in 1,428,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CDKN1C NM_001122630.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.01

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.938

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKN1C	NM_001122630.2	c.185G>T	p.Gly62Val	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.185G>T	p.Gly62Val	missense_variant	Exon 2 of 4	1	NM_001122630.2	ENSP00000411257.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1428184 Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1 AN XY: 707856

Gnomad4 AFR exome AF: 0.0000306

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.12e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;T;.;T;.
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.81	.;T;T;.;T
M_CAP	Pathogenic	0.99	D
MetaRNN	Pathogenic	0.94	D;D;D;D;D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Uncertain	2.4	M;M;.;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.8	D;D;D;D;.
REVEL	Pathogenic	0.70
Sift	Pathogenic	0.0	D;D;D;D;.
Sift4G	Uncertain	0.011	D;D;D;D;.
Polyphen		1.0	D;D;.;D;.
Vest4		0.50
MutPred		0.80		Loss of disorder (P = 0.0462);Loss of disorder (P = 0.0462);.;.;.;
MVP		0.78
MPC		2.8
ClinPred		0.98	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.56
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-2906502;