Genetic Variant CNDP2:c.-38+2C>T (chr18-74495925-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 4P and 8B. PVS1_StrongBA1

The ENST00000581272.5(CNDP2):c.-38+2C>T variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,362 control chromosomes in the GnomAD database, including 14,149 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 14113 hom., cov: 32)

Exomes 𝑓: 0.50 ( 36 hom. )

Consequence

CNDP2
ENST00000581272.5 splice_donor, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Publications

5 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: Likely_benign. The variant received -4 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.26865673 fraction of the gene. Cryptic splice site detected, with MaxEntScore 6.6, offset of 0 (no position change), new splice context is: cagGTgact. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNDP2	ENST00000581272.5 link	c.-38+2C>T		splice_donor_variant, intron_variant	Intron 1 of 4	4		ENSP00000464151.1		J3QRD0

Frequencies

GnomAD3 genomes

AF:

0.425

AC:

64594

AN:

151966

Hom.:

14103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.454

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.685

Gnomad SAS

AF:

0.451

Gnomad FIN

AF:

0.415

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.447

Gnomad OTH

AF:

0.423

GnomAD4 exome

AF:

0.496

AC:

138

AN:

278

Hom.:

Cov.:

AF XY:

0.500

AC XY:

107

AN XY:

214

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.833

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.487

AC:

113

AN:

232

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.425

AC:

64629

AN:

152084

Hom.:

14113

Cov.:

AF XY:

0.427

AC XY:

31729

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.333

AC:

13822

AN:

41508

American (AMR)

AF:

0.453

AC:

6928

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

1888

AN:

3470

East Asian (EAS)

AF:

0.684

AC:

3521

AN:

5146

South Asian (SAS)

AF:

0.452

AC:

2178

AN:

4818

European-Finnish (FIN)

AF:

0.415

AC:

4385

AN:

10576

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.447

AC:

30395

AN:

67968

Other (OTH)

AF:

0.427

AC:

901

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1894

3787

5681

7574

9468

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<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:

0.431

Hom.:

1884

Bravo

AF:

0.426

Asia WGS

AF:

0.520

AC:

1805

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.1

(source)

DANN

Benign

0.81

PhyloP100

-1.6

PromoterAI

-0.11

Neutral

(source)

Splicing

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