dbSNP rs34916325: CNDP2:p.Arg180Gln (chr18-74510895-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018235.3(CNDP2):c.539G>A(p.Arg180Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,614,076 control chromosomes in the GnomAD database, including 217 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.020 ( 107 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 110 hom. )

Consequence

CNDP2
NM_018235.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.252

Publications

6 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020300448).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNDP2	NM_018235.3 link	c.539G>A	p.Arg180Gln	missense_variant	Exon 6 of 12	ENST00000324262.9	NP_060705.2	Q96KP4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNDP2	ENST00000324262.9 link	c.539G>A	p.Arg180Gln	missense_variant	Exon 6 of 12	1	NM_018235.3	ENSP00000325548.4		Q96KP4-1

Frequencies

GnomAD3 genomes

AF:

0.0199

AC:

3034

AN:

152120

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00662

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.00534

AC:

1344

AN:

251484

AF XY:

0.00391

show subpopulations

Gnomad AFR exome

AF:

0.0749

Gnomad AMR exome

AF:

0.00275

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00205

AC:

3004

AN:

1461838

Hom.:

110

Cov.:

AF XY:

0.00178

AC XY:

1294

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.0745

AC:

2493

AN:

33480

American (AMR)

AF:

0.00335

AC:

150

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000197

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00243

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000728

AC:

AN:

1111966

Other (OTH)

AF:

0.00411

AC:

248

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

152

305

457

610

762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0199

AC:

3030

AN:

152238

Hom.:

107

Cov.:

AF XY:

0.0200

AC XY:

1489

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0697

AC:

2893

AN:

41520

American (AMR)

AF:

0.00661

AC:

101

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68028

Other (OTH)

AF:

0.0118

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

153

306

458

611

764

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00712

Hom.:

Bravo

AF:

0.0228

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0729

AC:

321

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00658

AC:

799

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.41

CADD

Benign

0.18

(source)

DANN

Benign

0.47

DEOGEN2

Benign

0.12

T;.;T;.;T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.50

.;T;T;T;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;N;.;.;.;.

PhyloP100

0.25

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.0

N;.;.;.;.;N;.

REVEL

Benign

0.026

Sift

Benign

0.17

T;.;.;.;.;T;.

Sift4G

Benign

0.21

T;T;T;T;T;T;T

Polyphen

0.0080

B;.;B;.;.;B;.

Vest4

0.14

MVP

0.47

MPC

0.19

ClinPred

0.0015

GERP RS

-2.8

PromoterAI

0.0067

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.065

gMVP

0.68

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over