rs6065945

chr20-46292992-C-G

Variant summary

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

The NM_021248.3(CDH22):c.-400+15263G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,348 control chromosomes in the GnomAD database, including 27,711 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 0.60 (27711 hom., cov: 29)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.591

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH22	NM_021248.3	c.-400+15263G>C		intron_variant		ENST00000537909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH22	ENST00000537909.4	c.-400+15263G>C		intron_variant		2	NM_021248.3	P1

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90184 AN: 151230 Hom.: 27664 Cov.: 29

Gnomad AFR AF: 0.730

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.714

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.597 AC: 90285 AN: 151348 Hom.: 27711 Cov.: 29 AF XY: 0.601 AC XY: 44377 AN XY: 73898

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.714

Gnomad4 FIN AF: 0.585

Gnomad4 NFE AF: 0.515

Gnomad4 OTH AF: 0.552

Alfa AF: 0.564 Hom.: 3043

Bravo AF: 0.600

Asia WGS AF: 0.689 AC: 2397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.45
Dann	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6065945; hg19: chr20-44921631;