18-74519169-G-C

Variant names:

• chr18-74519169-G-C
• rs2241508
• NM_018235.3:c.1358+73G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018235.3(CNDP2):​c.1358+73G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000074 in 1,351,222 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000074 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNDP2 NM_018235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

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.1358+73G>C		intron	N/A	NP_060705.2
	CNDP2	NM_001370248.1		c.1358+73G>C		intron	N/A	NP_001357177.1
	CNDP2	NM_001370249.1		c.1358+73G>C		intron	N/A	NP_001357178.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNDP2	ENST00000324262.9	TSL:1 MANE Select	c.1358+73G>C		intron	N/A	ENSP00000325548.4
	CNDP2	ENST00000324301.12	TSL:1	c.1106+73G>C		intron	N/A	ENSP00000325756.8
	CNDP2	ENST00000579847.5	TSL:5	c.1358+73G>C		intron	N/A	ENSP00000462311.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151720 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000740 AC: 10 AN: 1351222 Hom.: 0 AF XY: 0.00000454 AC XY: 3 AN XY: 660398

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30260

American (AMR) AF: 0.00 AC: 0 AN: 30736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20102

East Asian (EAS) AF: 0.0000263 AC: 1 AN: 38028

South Asian (SAS) AF: 0.0000143 AC: 1 AN: 69828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3826

European-Non Finnish (NFE) AF: 0.00000758 AC: 8 AN: 1055554

Other (OTH) AF: 0.00 AC: 0 AN: 55500

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151838 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74230

African (AFR) AF: 0.00 AC: 0 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15264

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67924

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 54430

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.010
DANN	Benign	0.39
PhyloP100		-2.5

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: rs2241508; hg19: chr18-72186404;