rs2425785

chr20-46210683-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.1033-123C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 911,410 control chromosomes in the GnomAD database, including 61,225 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 0.39 (11771 hom., cov: 31)
  • Exomes 𝑓: 0.36 (49454 hom.)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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]

LOC124904916 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH22	NM_021248.3	c.1033-123C>G		intron_variant		ENST00000537909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH22	ENST00000537909.4	c.1033-123C>G		intron_variant		2	NM_021248.3	P1
CDH22	ENST00000474438.1	n.901-123C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58661 AN: 151774 Hom.: 11758 Cov.: 31

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.358 AC: 271586 AN: 759518 Hom.: 49454 AF XY: 0.360 AC XY: 135163 AN XY: 375692

Gnomad4 AFR exome AF: 0.487

Gnomad4 AMR exome AF: 0.308

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.280

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.352

Gnomad4 OTH exome AF: 0.361

GnomAD4 genome AF: 0.387 AC: 58717 AN: 151892 Hom.: 11771 Cov.: 31 AF XY: 0.382 AC XY: 28369 AN XY: 74236

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.365

Alfa AF: 0.365 Hom.: 1260

Bravo AF: 0.385

Asia WGS AF: 0.360 AC: 1254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.12
Dann	Benign	0.67

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: rs2425785; hg19: chr20-44839322;