chr18-74510895-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018235.3(CNDP2):​c.539G>A​(p.Arg180Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00374 in 1,614,076 control chromosomes in the GnomAD database, including 217 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.020 (107 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (110 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020300448).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0676 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.539G>A	p.Arg180Gln	missense	Exon 6 of 12	NP_060705.2
	CNDP2	NM_001370248.1		c.539G>A	p.Arg180Gln	missense	Exon 6 of 12	NP_001357177.1
	CNDP2	NM_001370249.1		c.539G>A	p.Arg180Gln	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>A	p.Arg180Gln	missense	Exon 6 of 12	ENSP00000325548.4
	CNDP2	ENST00000324301.12	TSL:1	c.287G>A	p.Arg96Gln	missense	Exon 3 of 9	ENSP00000325756.8
	CNDP2	ENST00000579847.5	TSL:5	c.539G>A	p.Arg180Gln	missense	Exon 6 of 12	ENSP00000462311.1

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3034 AN: 152120 Hom.: 107 Cov.: 33

Gnomad AFR AF: 0.0700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00662

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00534 AC: 1344 AN: 251484 AF XY: 0.00391

Gnomad AFR exome AF: 0.0749

Gnomad AMR exome AF: 0.00275

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00205 AC: 3004 AN: 1461838 Hom.: 110 Cov.: 31 AF XY: 0.00178 AC XY: 1294 AN XY: 727218

African (AFR) AF: 0.0745 AC: 2493 AN: 33480

American (AMR) AF: 0.00335 AC: 150 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26134

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

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5768

European-Non Finnish (NFE) AF: 0.0000728 AC: 81 AN: 1111966

Other (OTH) AF: 0.00411 AC: 248 AN: 60394

GnomAD4 genome AF: 0.0199 AC: 3030 AN: 152238 Hom.: 107 Cov.: 33 AF XY: 0.0200 AC XY: 1489 AN XY: 74406

African (AFR) AF: 0.0697 AC: 2893 AN: 41520

American (AMR) AF: 0.00661 AC: 101 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68028

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.00712 Hom.: 89

Bravo AF: 0.0228

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.0729 AC: 321

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00658 AC: 799

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.18
DANN	Benign	0.47
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.087	N
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.25
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.026
Sift	Benign	0.17	T
Sift4G	Benign	0.21	T
Polyphen		0.0080	B
Vest4		0.14
MVP		0.47
MPC		0.19
ClinPred		0.0015	T
GERP RS		-2.8
PromoterAI		0.0067	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.065
gMVP		0.68
Mutation Taster		=96/4	polymorphism (auto)

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; COSMIC: COSV60839815; COSMIC: COSV60839815;