rs2425807

Variant names:

• chr20-46252906-A-G
• rs2425807
• NM_021248.3:c.-399-1213T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021248.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH22	NM_021248.3	MANE Select	c.-399-1213T>C		intron	N/A	NP_067071.1	Q9UJ99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH22	ENST00000537909.4	TSL:2 MANE Select	c.-399-1213T>C		intron	N/A	ENSP00000437790.1	Q9UJ99
	CDH22	ENST00000946368.1		c.-399-1213T>C		intron	N/A	ENSP00000616427.1
	CDH22	ENST00000946369.1		c.-399-1213T>C		intron	N/A	ENSP00000616428.1

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

African (AFR) AF: 0.371 AC: 15384 AN: 41482

American (AMR) AF: 0.396 AC: 6056 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 1505 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1241 AN: 5180

South Asian (SAS) AF: 0.263 AC: 1267 AN: 4816

European-Finnish (FIN) AF: 0.393 AC: 4151 AN: 10562

Middle Eastern (MID) AF: 0.640 AC: 187 AN: 292

European-Non Finnish (NFE) AF: 0.433 AC: 29457 AN: 67966

Other (OTH) AF: 0.423 AC: 891 AN: 2106

Alfa AF: 0.423 Hom.: 25168

Bravo AF: 0.399

Asia WGS AF: 0.261 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.3
DANN	Benign	0.57
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2425807; hg19: chr20-44881545;