rs6566811

Positions:

• chr18-74496357-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000580672.5(CNDP2):​c.76G>A​(p.Gly26Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,208 control chromosomes in the GnomAD database, including 13,041 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 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 0.41 (13026 hom., cov: 33)
  • Exomes 𝑓: 0.40 (15 hom.)
• Consequence: CNDP2 ENST00000580672.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0119554E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNDP2	NM_018235.3			upstream_gene_variant		ENST00000324262.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNDP2	ENST00000324262.9			upstream_gene_variant		1	NM_018235.3	P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62065 AN: 151934 Hom.: 13016 Cov.: 33

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.408

GnomAD3 exomes AF: 0.477 AC: 453 AN: 950 Hom.: 119 AF XY: 0.500 AC XY: 208 AN XY: 416

Gnomad ASJ exome AF: 1.00

Gnomad NFE exome AF: 0.477

Gnomad OTH exome AF: 0.333

GnomAD4 exome AF: 0.404 AC: 63 AN: 156 Hom.: 15 Cov.: 0 AF XY: 0.392 AC XY: 47 AN XY: 120

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.403

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.408 AC: 62098 AN: 152052 Hom.: 13026 Cov.: 33 AF XY: 0.409 AC XY: 30422 AN XY: 74332

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.534

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.412

Alfa AF: 0.426 Hom.: 17581

Bravo AF: 0.411

TwinsUK AF: 0.422 AC: 1563

ALSPAC AF: 0.427 AC: 1645

ExAC AF: 0.158 AC: 404

Asia WGS AF: 0.517 AC: 1793 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	11
DANN	Benign	0.85
FATHMM_MKL	Benign	0.0054	N
LIST_S2	Benign	0.27	T
MetaRNN	Benign	0.0000010	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Uncertain	0.61	T
Sift4G	Benign	0.13	T
GERP RS		-5.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs6566811; hg19: chr18-72163592; COSMIC: COSV60840447; COSMIC: COSV60840447;