chr18-74510895-G-C

Variant names:

• chr18-74510895-G-C
• rs34916325
• NM_018235.3:c.539G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018235.3(CNDP2):​c.539G>C​(p.Arg180Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CNDP2 NM_018235.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 6 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018235.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNDP2	NM_018235.3	MANE Select	c.539G>C	p.Arg180Pro	missense	Exon 6 of 12	NP_060705.2
	CNDP2	NM_001370248.1		c.539G>C	p.Arg180Pro	missense	Exon 6 of 12	NP_001357177.1
	CNDP2	NM_001370249.1		c.539G>C	p.Arg180Pro	missense	Exon 8 of 14	NP_001357178.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNDP2	ENST00000324262.9	TSL:1 MANE Select	c.539G>C	p.Arg180Pro	missense	Exon 6 of 12	ENSP00000325548.4
	CNDP2	ENST00000324301.12	TSL:1	c.287G>C	p.Arg96Pro	missense	Exon 3 of 9	ENSP00000325756.8
	CNDP2	ENST00000579847.5	TSL:5	c.539G>C	p.Arg180Pro	missense	Exon 6 of 12	ENSP00000462311.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251484 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461838 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727218

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111966

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	4.3
DANN	Benign	0.35
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.25
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.20
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.059	T
Polyphen		0.021	B
Vest4		0.47
MutPred		0.66		Loss of stability (P = 0.0243)
MVP		0.68
MPC		0.47
ClinPred		0.85	D
GERP RS		-2.8
PromoterAI		-0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.72
gMVP		0.94

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

Other links and lift over

dbSNP: rs34916325; hg19: chr18-72178130;