18-74501373-G-A

Variant names:

• chr18-74501373-G-A
• rs2303463
• NM_018235.3:c.105G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018235.3(CNDP2):​c.105G>A​(p.Pro35Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,613,618 control chromosomes in the GnomAD database, including 34,642 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 0.21 (3456 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31186 hom.)
• Consequence: CNDP2 NM_018235.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -8.34
• Publications: 36 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-8.34 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

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.105G>A	p.Pro35Pro	synonymous	Exon 3 of 12	NP_060705.2
	CNDP2	NM_001370248.1		c.105G>A	p.Pro35Pro	synonymous	Exon 3 of 12	NP_001357177.1
	CNDP2	NM_001370249.1		c.105G>A	p.Pro35Pro	synonymous	Exon 5 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.105G>A	p.Pro35Pro	synonymous	Exon 3 of 12	ENSP00000325548.4
	CNDP2	ENST00000324301.12	TSL:1	c.105G>A	p.Pro35Pro	synonymous	Exon 2 of 9	ENSP00000325756.8
	CNDP2	ENST00000584768.5	TSL:1	c.105G>A	p.Pro35Pro	synonymous	Exon 2 of 4	ENSP00000482227.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31622 AN: 151960 Hom.: 3444 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.214

GnomAD2 exomes AF: 0.218 AC: 54743 AN: 251172 AF XY: 0.216

Gnomad AFR exome AF: 0.226

Gnomad AMR exome AF: 0.342

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.293

Gnomad FIN exome AF: 0.115

Gnomad NFE exome AF: 0.187

Gnomad OTH exome AF: 0.200

GnomAD4 exome AF: 0.202 AC: 294983 AN: 1461538 Hom.: 31186 Cov.: 33 AF XY: 0.203 AC XY: 147341 AN XY: 727088

African (AFR) AF: 0.225 AC: 7515 AN: 33470

American (AMR) AF: 0.339 AC: 15151 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 3724 AN: 26122

East Asian (EAS) AF: 0.293 AC: 11625 AN: 39666

South Asian (SAS) AF: 0.246 AC: 21208 AN: 86206

European-Finnish (FIN) AF: 0.119 AC: 6373 AN: 53416

Middle Eastern (MID) AF: 0.204 AC: 1176 AN: 5756

European-Non Finnish (NFE) AF: 0.195 AC: 216582 AN: 1111868

Other (OTH) AF: 0.193 AC: 11629 AN: 60372

GnomAD4 genome AF: 0.208 AC: 31655 AN: 152080 Hom.: 3456 Cov.: 32 AF XY: 0.210 AC XY: 15603 AN XY: 74350

African (AFR) AF: 0.222 AC: 9189 AN: 41474

American (AMR) AF: 0.292 AC: 4457 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3470

East Asian (EAS) AF: 0.286 AC: 1477 AN: 5162

South Asian (SAS) AF: 0.249 AC: 1199 AN: 4820

European-Finnish (FIN) AF: 0.116 AC: 1230 AN: 10578

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12959 AN: 67980

Other (OTH) AF: 0.214 AC: 453 AN: 2114

Alfa AF: 0.200 Hom.: 9611

Bravo AF: 0.220

Asia WGS AF: 0.288 AC: 1004 AN: 3478

EpiCase AF: 0.188

EpiControl AF: 0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_noAF	Benign	-0.73
CADD	Benign	1.2
DANN	Benign	0.82
PhyloP100		-8.3
PromoterAI		-0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2303463; hg19: chr18-72168608; COSMIC: COSV60838835; COSMIC: COSV60838835;