chr19-40223428-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024877.4(CCNP):​c.632G>A​(p.Cys211Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000216 in 1,600,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

CCNP
NM_024877.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80
Variant links:
Genes affected
CCNP (HGNC:25805): (cyclin P) Predicted to enable cyclin-dependent protein serine/threonine kinase regulator activity. Predicted to be involved in mitotic cell cycle phase transition and regulation of cyclin-dependent protein serine/threonine kinase activity. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.254906).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCNPNM_024877.4 linkc.632G>A p.Cys211Tyr missense_variant Exon 4 of 5 ENST00000430325.7 NP_079153.2 Q9H8S5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCNPENST00000430325.7 linkc.632G>A p.Cys211Tyr missense_variant Exon 4 of 5 2 NM_024877.4 ENSP00000396755.2 Q9H8S5-1

Frequencies

GnomAD3 genomes
AF:
0.000105
AC:
16
AN:
152248
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.000176
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000952
AC:
21
AN:
220474
Hom.:
0
AF XY:
0.0000822
AC XY:
10
AN XY:
121622
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000307
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000208
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000227
AC:
329
AN:
1448354
Hom.:
0
Cov.:
31
AF XY:
0.000233
AC XY:
168
AN XY:
719670
show subpopulations
Gnomad4 AFR exome
AF:
0.0000302
Gnomad4 AMR exome
AF:
0.0000232
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:
0.000288
Gnomad4 OTH exome
AF:
0.000134
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
152248
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000931
Hom.:
0
Bravo
AF:
0.000102
ExAC
AF:
0.0000931
AC:
11

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 13, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.632G>A (p.C211Y) alteration is located in exon 4 (coding exon 4) of the CNTD2 gene. This alteration results from a G to A substitution at nucleotide position 632, causing the cysteine (C) at amino acid position 211 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.57
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.41
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.040
T;.;.
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.22
FATHMM_MKL
Benign
0.69
D
LIST_S2
Benign
0.59
T;T;T
M_CAP
Benign
0.043
D
MetaRNN
Benign
0.25
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.045
N;.;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
1.2
N;.;N
REVEL
Benign
0.22
Sift
Uncertain
0.012
D;.;D
Sift4G
Benign
0.32
T;.;T
Vest4
0.64
MVP
0.63
MPC
2.0
ClinPred
0.24
T
GERP RS
4.0
Varity_R
0.25
gMVP
0.69

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

LitVar

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

Other links and lift over

dbSNP: rs761118637; hg19: chr19-40729335; API