20-46191225-T-C

Position:

• chr20-46191225-T-C

Variant summary

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

The NM_021248.3(CDH22):​c.1424-4278A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 151,948 control chromosomes in the GnomAD database, including 6,169 homozygotes. 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 0.20 (6169 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.64

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH22	NM_021248.3	c.1424-4278A>G		intron_variant		ENST00000537909.4
CDH22	XM_011528994.3	c.1424-4278A>G		intron_variant
CDH22	XM_024451966.2	c.1061-4278A>G		intron_variant
CDH22	XM_047440373.1	c.1423+8198A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH22	ENST00000537909.4	c.1424-4278A>G		intron_variant		2	NM_021248.3	P1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29651 AN: 151830 Hom.: 6143 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0113

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0419

Gnomad OTH AF: 0.153

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.196 AC: 29721 AN: 151948 Hom.: 6169 Cov.: 32 AF XY: 0.195 AC XY: 14480 AN XY: 74276

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.0113

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0237

Gnomad4 NFE AF: 0.0419

Gnomad4 OTH AF: 0.151

Alfa AF: 0.0614 Hom.: 850

Bravo AF: 0.223

Asia WGS AF: 0.282 AC: 978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.12
DANN	Benign	0.30

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: rs4383400; hg19: chr20-44819864;