18-74500019-G-A

Position:

• chr18-74500019-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018235.3(CNDP2):​c.46G>A​(p.Asp16Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: CNDP2 NM_018235.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.30

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3354122).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNDP2	NM_018235.3	c.46G>A	p.Asp16Asn	missense_variant	2/12	ENST00000324262.9	NP_060705.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNDP2	ENST00000324262.9	c.46G>A	p.Asp16Asn	missense_variant	2/12	1	NM_018235.3	ENSP00000325548.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Jul 31, 2024

The c.46G>A (p.D16N) alteration is located in exon 2 (coding exon 1) of the CNDP2 gene. This alteration results from a G to A substitution at nucleotide position 46, causing the aspartic acid (D) at amino acid position 16 to be replaced by an asparagine (N). 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	0.12
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T;T;T;T;.;T;.;T;T;.;T;T;.;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.86	D;.;D;T;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.34	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;L;L;.;.;.;.;.;.;.;.;.;L;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.50	.;N;.;.;.;.;.;.;.;.;.;.;N;.
REVEL	Benign	0.094
Sift	Benign	0.21	.;T;.;.;.;.;.;.;.;.;.;.;T;.
Sift4G	Benign	0.36	T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0, 0.93	.;B;B;.;.;.;.;.;.;.;.;.;P;.
Vest4		0.41, 0.42, 0.51, 0.41
MutPred		0.49		Gain of MoRF binding (P = 0.0348);Gain of MoRF binding (P = 0.0348);Gain of MoRF binding (P = 0.0348);Gain of MoRF binding (P = 0.0348);Gain of MoRF binding (P = 0.0348);Gain of MoRF binding (P = 0.0348);Gain of MoRF binding (P = 0.0348);Gain of MoRF binding (P = 0.0348);Gain of MoRF binding (P = 0.0348);Gain of MoRF binding (P = 0.0348);Gain of MoRF binding (P = 0.0348);Gain of MoRF binding (P = 0.0348);Gain of MoRF binding (P = 0.0348);Gain of MoRF binding (P = 0.0348);
MVP		0.70
MPC		0.16
ClinPred		0.76	D
GERP RS		5.4
Varity_R		0.24
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-72167254;