rs6065945

Variant names:

• chr20-46292992-C-G
• rs6065945
• NM_021248.3:c.-400+15263G>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.-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
• Publications: 7 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=-0.81).
• 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 rank	MANE	Protein	UniProt
CDH22	NM_021248.3	c.-400+15263G>C		intron_variant	Intron 1 of 11	ENST00000537909.4	NP_067071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH22	ENST00000537909.4	c.-400+15263G>C		intron_variant	Intron 1 of 11	2	NM_021248.3	ENSP00000437790.1

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

African (AFR) AF: 0.730 AC: 30054 AN: 41182

American (AMR) AF: 0.595 AC: 9059 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1800 AN: 3466

East Asian (EAS) AF: 0.620 AC: 3197 AN: 5160

South Asian (SAS) AF: 0.714 AC: 3413 AN: 4782

European-Finnish (FIN) AF: 0.585 AC: 6071 AN: 10376

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34981 AN: 67864

Other (OTH) AF: 0.552 AC: 1159 AN: 2100

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
PhyloP100		-0.59
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: rs6065945; hg19: chr20-44921631;