Variant chr18-74508924-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018235.3(CNDP2):c.452G>T(p.Gly151Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000328 in 1,613,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

CNDP2
NM_018235.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.191

Variant links:

Genes affected

CNDP2 (HGNC:24437): (carnosine dipeptidase 2) CNDP2, also known as tissue carnosinase and peptidase A (EC 3.4.13.18), is a nonspecific dipeptidase rather than a selective carnosinase (Teufel et al., 2003 [PubMed 12473676]).[supplied by OMIM, Mar 2008]

CNDP2 links:

CNDP2 (HGNC:):

CNDP2 links:

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=0.094555646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNDP2	NM_018235.3 linkuse as main transcript	c.452G>T	p.Gly151Val	missense_variant	5/12	ENST00000324262.9	NP_060705.2	Q96KP4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNDP2	ENST00000324262.9 linkuse as main transcript	c.452G>T	p.Gly151Val	missense_variant	5/12	1	NM_018235.3	ENSP00000325548.4		Q96KP4-1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000239

AC:

AN:

251100

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000502

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000337

AC:

492

AN:

1461562

Hom.:

Cov.:

AF XY:

0.000315

AC XY:

229

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000432

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000243

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000319

Hom.:

Bravo

AF:

0.000246

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2022

The c.452G>T (p.G151V) alteration is located in exon 5 (coding exon 4) of the CNDP2 gene. This alteration results from a G to T substitution at nucleotide position 452, causing the glycine (G) at amino acid position 151 to be replaced by a valine (V). 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

Benign

0.34

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.0

DANN

Benign

0.37

DEOGEN2

Uncertain

0.48

T;.;T;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.92

.;D;D;D;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.095

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.5

M;.;M;.;.;.

PrimateAI

Benign

0.28

PROVEAN

Pathogenic

-5.6

D;.;.;.;.;.

REVEL

Benign

0.17

Sift

Uncertain

0.0010

D;.;.;.;.;.

Sift4G

Uncertain

0.024

D;D;D;T;D;D

Polyphen

0.48

P;.;P;.;.;.

Vest4

0.37

MVP

0.24

MPC

0.25

ClinPred

0.24

GERP RS

-5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.47

gMVP

0.60

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over