18-74500006-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018235.3(CNDP2):c.33A>G(p.Ile11Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CNDP2 NM_018235.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.26

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]

ACMG classification

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=0.2343587).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNDP2	NM_018235.3	c.33A>G	p.Ile11Met	missense_variant	2/12	ENST00000324262.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNDP2	ENST00000324262.9	c.33A>G	p.Ile11Met	missense_variant	2/12	1	NM_018235.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 11, 2022

The c.33A>G (p.I11M) alteration is located in exon 2 (coding exon 1) of the CNDP2 gene. This alteration results from a A to G substitution at nucleotide position 33, causing the isoleucine (I) at amino acid position 11 to be replaced by a methionine (M). 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	Uncertain	0.35
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	14
Dann	Benign	0.46
DEOGEN2	Benign	0.10	T;T;T;T;.;T;.;T;T;.;T;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.027	N
LIST_S2	Uncertain	0.87	D;.;D;T;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.23	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.63	D;D;N
PrimateAI	Benign	0.33	T
Sift4G	Uncertain	0.0020	D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.48, 0.74	.;P;P;.;.;.;.;.;.;.;.;.;P;.
Vest4		0.36, 0.45, 0.33, 0.45
MutPred		0.65		Gain of phosphorylation at Y10 (P = 0.0605);Gain of phosphorylation at Y10 (P = 0.0605);Gain of phosphorylation at Y10 (P = 0.0605);Gain of phosphorylation at Y10 (P = 0.0605);Gain of phosphorylation at Y10 (P = 0.0605);Gain of phosphorylation at Y10 (P = 0.0605);Gain of phosphorylation at Y10 (P = 0.0605);Gain of phosphorylation at Y10 (P = 0.0605);Gain of phosphorylation at Y10 (P = 0.0605);Gain of phosphorylation at Y10 (P = 0.0605);Gain of phosphorylation at Y10 (P = 0.0605);Gain of phosphorylation at Y10 (P = 0.0605);Gain of phosphorylation at Y10 (P = 0.0605);Gain of phosphorylation at Y10 (P = 0.0605);
MVP		0.19
MPC		0.41
ClinPred		0.96	D
GERP RS		-11
Varity_R		0.74
gMVP		0.68

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

Other links and lift over

dbSNP: rs1978605892; hg19: chr18-72167241;