20-46174860-G-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_021248.3(CDH22):c.2133C>G(p.Gly711=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 22)
  • Exomes 𝑓: 0.024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDH22 NM_021248.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.368

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 Benign. Variant got -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 20-46174860-G-C is Benign according to our data. Variant chr20-46174860-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2652367.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.368 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH22	NM_021248.3	c.2133C>G	p.Gly711=	synonymous_variant	12/12	ENST00000537909.4
CDH22	XM_011528994.3	c.2133C>G	p.Gly711=	synonymous_variant	12/12
CDH22	XM_047440373.1	c.1893C>G	p.Gly631=	synonymous_variant	10/10
CDH22	XM_024451966.2	c.1770C>G	p.Gly590=	synonymous_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH22	ENST00000537909.4	c.2133C>G	p.Gly711=	synonymous_variant	12/12	2	NM_021248.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 14 AN: 68058 Hom.: 0 Cov.: 22 FAILED QC

Gnomad AFR AF: 0.000165

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000148

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000371

Gnomad SAS AF: 0.00142

Gnomad FIN AF: 0.000276

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000127

Gnomad OTH AF: 0.00115

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0235 AC: 3391 AN: 144222 Hom.: 0 Cov.: 4 AF XY: 0.0198 AC XY: 1490 AN XY: 75326

Gnomad4 AFR exome AF: 0.0192

Gnomad4 AMR exome AF: 0.00126

Gnomad4 ASJ exome AF: 0.00457

Gnomad4 EAS exome AF: 0.00482

Gnomad4 SAS exome AF: 0.00495

Gnomad4 FIN exome AF: 0.000400

Gnomad4 NFE exome AF: 0.0308

Gnomad4 OTH exome AF: 0.0207

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000206 AC: 14 AN: 68058 Hom.: 0 Cov.: 22 AF XY: 0.000297 AC XY: 10 AN XY: 33614

Gnomad4 AFR AF: 0.000165

Gnomad4 AMR AF: 0.000148

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000372

Gnomad4 SAS AF: 0.00142

Gnomad4 FIN AF: 0.000276

Gnomad4 NFE AF: 0.000127

Gnomad4 OTH AF: 0.00114

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

CDH22: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.2
Dann	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs772485362; hg19: chr20-44803499;