20-46282460-A-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH22	NM_021248.3	c.-400+25795T>A		intron_variant		ENST00000537909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH22	ENST00000537909.4	c.-400+25795T>A		intron_variant		2	NM_021248.3	P1

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

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.526

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.537

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
Cadd	Benign	16
Dann	Benign	0.86

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2425855; hg19: chr20-44911099;