chr2-219172995-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015680.6(CNPPD1):​c.824G>A​(p.Arg275His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R275C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

CNPPD1
NM_015680.6 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.238
Variant links:
Genes affected
CNPPD1 (HGNC:25220): (cyclin Pas1/PHO80 domain containing 1) Predicted to enable cyclin-dependent protein serine/threonine kinase regulator activity. Predicted to be involved in regulation of cyclin-dependent protein serine/threonine kinase activity. Predicted to be integral component of membrane. Predicted to be part of cyclin-dependent protein kinase holoenzyme complex. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.022321016).
BP6
Variant 2-219172995-C-T is Benign according to our data. Variant chr2-219172995-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3834587.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNPPD1NM_015680.6 linkc.824G>A p.Arg275His missense_variant Exon 8 of 8 ENST00000360507.10 NP_056495.4 Q9BV87A0A024R432

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNPPD1ENST00000360507.10 linkc.824G>A p.Arg275His missense_variant Exon 8 of 8 1 NM_015680.6 ENSP00000353698.5 Q9BV87
CNPPD1ENST00000409789.5 linkc.824G>A p.Arg275His missense_variant Exon 9 of 9 1 ENSP00000386277.1 Q9BV87
CNPPD1ENST00000453038.5 linkc.824G>A p.Arg275His missense_variant Exon 9 of 9 2 ENSP00000410109.1 C9JF31
CNPPD1ENST00000451647.1 linkc.*56G>A downstream_gene_variant 3 ENSP00000405997.1 C9J597

Frequencies

GnomAD3 genomes
AF:
0.000210
AC:
32
AN:
152072
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000628
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000519
AC:
13
AN:
250550
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135542
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.000203
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:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461632
Hom.:
0
Cov.:
71
AF XY:
0.0000138
AC XY:
10
AN XY:
727104
show subpopulations
Gnomad4 AFR exome
AF:
0.000448
Gnomad4 AMR exome
AF:
0.000224
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:
0.00000270
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.000210
AC:
32
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.000188
AC XY:
14
AN XY:
74400
show subpopulations
Gnomad4 AFR
AF:
0.000626
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000966
Hom.:
0
Bravo
AF:
0.000178
ExAC
AF:
0.0000659
AC:
8

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jan 17, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.075
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
8.5
DANN
Benign
0.94
DEOGEN2
Benign
0.0026
T;T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.057
N
LIST_S2
Benign
0.63
.;T;T
M_CAP
Benign
0.0055
T
MetaRNN
Benign
0.022
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;N;.
PrimateAI
Benign
0.19
T
PROVEAN
Benign
-0.49
N;N;N
REVEL
Benign
0.019
Sift
Benign
0.15
T;T;T
Sift4G
Benign
0.12
T;T;.
Polyphen
0.47
P;P;.
Vest4
0.032
MVP
0.076
MPC
0.28
ClinPred
0.0071
T
GERP RS
0.63
Varity_R
0.019
gMVP
0.21

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: rs201528705; hg19: chr2-220037717; API