20-46195985-A-G

Variant names:

• chr20-46195985-A-G
• rs2868767
• NM_021248.3:c.1423+3438T>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.1423+3438T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,084 control chromosomes in the GnomAD database, including 7,302 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 0.27 (7302 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH22	NM_021248.3	c.1423+3438T>C		intron_variant	Intron 8 of 11	ENST00000537909.4	NP_067071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH22	ENST00000537909.4	c.1423+3438T>C		intron_variant	Intron 8 of 11	2	NM_021248.3	ENSP00000437790.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41299 AN: 151964 Hom.: 7272 Cov.: 32

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.272 AC: 41388 AN: 152084 Hom.: 7302 Cov.: 32 AF XY: 0.272 AC XY: 20227 AN XY: 74342

African (AFR) AF: 0.505 AC: 20932 AN: 41476

American (AMR) AF: 0.249 AC: 3800 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3470

East Asian (EAS) AF: 0.310 AC: 1596 AN: 5154

South Asian (SAS) AF: 0.223 AC: 1076 AN: 4820

European-Finnish (FIN) AF: 0.146 AC: 1541 AN: 10590

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 10991 AN: 67970

Other (OTH) AF: 0.248 AC: 524 AN: 2114

Alfa AF: 0.207 Hom.: 11593

Bravo AF: 0.294

Asia WGS AF: 0.302 AC: 1048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.023
DANN	Benign	0.23
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2868767; hg19: chr20-44824624;