20-46282460-A-T

Variant names:

• chr20-46282460-A-T
• rs2425855
• NM_021248.3:c.-400+25795T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021248.3(CDH22):​c.-400+25795T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 151,876 control chromosomes in the GnomAD database, including 25,308 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 0.57 (25308 hom., cov: 31)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.719 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH22	NM_021248.3	MANE Select	c.-400+25795T>A		intron	N/A	NP_067071.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH22	ENST00000537909.4	TSL:2 MANE Select	c.-400+25795T>A		intron	N/A	ENSP00000437790.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87026 AN: 151758 Hom.: 25266 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.574 AC: 87122 AN: 151876 Hom.: 25308 Cov.: 31 AF XY: 0.579 AC XY: 42962 AN XY: 74252

African (AFR) AF: 0.612 AC: 25319 AN: 41376

American (AMR) AF: 0.609 AC: 9288 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1825 AN: 3470

East Asian (EAS) AF: 0.646 AC: 3331 AN: 5160

South Asian (SAS) AF: 0.739 AC: 3558 AN: 4812

European-Finnish (FIN) AF: 0.586 AC: 6183 AN: 10558

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35922 AN: 67924

Other (OTH) AF: 0.537 AC: 1134 AN: 2112

Alfa AF: 0.549 Hom.: 2735

Bravo AF: 0.571

Asia WGS AF: 0.700 AC: 2435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	16
DANN	Benign	0.86
PhyloP100		1.3
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: rs2425855; hg19: chr20-44911099;