20-46238586-G-C

Position:

• chr20-46238586-G-C

Variant summary

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

The NM_021248.3(CDH22):​c.550+2377C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 152,028 control chromosomes in the GnomAD database, including 6,231 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 0.28 (6231 hom., cov: 33)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.149

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH22	NM_021248.3	c.550+2377C>G		intron_variant		ENST00000537909.4	NP_067071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH22	ENST00000537909.4	c.550+2377C>G		intron_variant		2	NM_021248.3	ENSP00000437790.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42744 AN: 151910 Hom.: 6229 Cov.: 33

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.281 AC: 42767 AN: 152028 Hom.: 6231 Cov.: 33 AF XY: 0.279 AC XY: 20736 AN XY: 74302

Gnomad4 AFR AF: 0.369

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.272

Alfa AF: 0.143 Hom.: 263

Bravo AF: 0.283

Asia WGS AF: 0.235 AC: 817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.9
DANN	Benign	0.65

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: rs966567; hg19: chr20-44867225;