rs2425809

Positions:

• chr20-46258961-C-T

Variant summary

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

The NM_021248.3(CDH22):​c.-399-7268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,058 control chromosomes in the GnomAD database, including 12,040 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 (12040 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH22	NM_021248.3	c.-399-7268G>A		intron_variant		ENST00000537909.4	NP_067071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH22	ENST00000537909.4	c.-399-7268G>A		intron_variant		2	NM_021248.3	ENSP00000437790	P1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58719 AN: 151940 Hom.: 12029 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.452

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.386 AC: 58749 AN: 152058 Hom.: 12040 Cov.: 32 AF XY: 0.386 AC XY: 28680 AN XY: 74332

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.409

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.415

Alfa AF: 0.416 Hom.: 5198

Bravo AF: 0.383

Asia WGS AF: 0.434 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2425809; hg19: chr20-44887600;