20-46174540-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021248.3(CDH22):c.2453G>T(p.Gly818Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDH22 NM_021248.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.25

Genes affected

CDH22 (HGNC:13251): (cadherin 22) This gene is a member of the cadherin superfamily. The gene product is composed of five cadherin repeat domains and a cytoplasmic tail similar to the highly conserved cytoplasmic region of classical cadherins. Expressed predominantly in the brain, this putative calcium-dependent cell adhesion protein may play an important role in morphogenesis and tissue formation in neural and non-neural cells during development and maintenance of the brain and neuroendocrine organs. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH22	NM_021248.3	c.2453G>T	p.Gly818Val	missense_variant	12/12	ENST00000537909.4
CDH22	XM_011528994.3	c.2453G>T	p.Gly818Val	missense_variant	12/12
CDH22	XM_047440373.1	c.2213G>T	p.Gly738Val	missense_variant	10/10
CDH22	XM_024451966.2	c.2090G>T	p.Gly697Val	missense_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH22	ENST00000537909.4	c.2453G>T	p.Gly818Val	missense_variant	12/12	2	NM_021248.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1369128 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 675440

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 05, 2022

The c.2453G>T (p.G818V) alteration is located in exon 11 (coding exon 11) of the CDH22 gene. This alteration results from a G to T substitution at nucleotide position 2453, causing the glycine (G) at amino acid position 818 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Pathogenic	0.91	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Uncertain	0.028	D
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-3.1	D;D
REVEL	Uncertain	0.54
Sift	Benign	0.16	T;T
Sift4G	Benign	0.13	T;T
Polyphen		1.0	D;D
Vest4		0.32
MutPred		0.54		Loss of disorder (P = 0.0087);Loss of disorder (P = 0.0087);
MVP		0.78
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.53
gMVP		0.58

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-44803179;