rs2425807

Positions:

• chr20-46252906-A-G

Variant summary

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

The NM_021248.3(CDH22):​c.-399-1213T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,068 control chromosomes in the GnomAD database, including 12,339 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 0.40 (12339 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH22	NM_021248.3	c.-399-1213T>C		intron_variant		ENST00000537909.4	NP_067071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH22	ENST00000537909.4	c.-399-1213T>C		intron_variant		2	NM_021248.3	ENSP00000437790.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60479 AN: 151950 Hom.: 12309 Cov.: 32

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.434

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.398 AC: 60546 AN: 152068 Hom.: 12339 Cov.: 32 AF XY: 0.394 AC XY: 29305 AN XY: 74332

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.434

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.423

Alfa AF: 0.429 Hom.: 18423

Bravo AF: 0.399

Asia WGS AF: 0.261 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.3
DANN	Benign	0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2425807; hg19: chr20-44881545;