NM_021248.3:c.-399-14954C>T

Variant names:

• chr20-46266647-G-A
• rs2425817
• NM_021248.3:c.-399-14954C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021248.3(CDH22):​c.-399-14954C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,092 control chromosomes in the GnomAD database, including 12,632 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 0.40 (12632 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410
• Publications: 3 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH22	NM_021248.3	c.-399-14954C>T		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.-399-14954C>T		intron_variant	Intron 1 of 11	2	NM_021248.3	ENSP00000437790.1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60680 AN: 151974 Hom.: 12611 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.399 AC: 60731 AN: 152092 Hom.: 12632 Cov.: 32 AF XY: 0.399 AC XY: 29703 AN XY: 74376

African (AFR) AF: 0.275 AC: 11388 AN: 41464

American (AMR) AF: 0.449 AC: 6864 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3470

East Asian (EAS) AF: 0.476 AC: 2461 AN: 5172

South Asian (SAS) AF: 0.413 AC: 1991 AN: 4824

European-Finnish (FIN) AF: 0.390 AC: 4122 AN: 10576

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30867 AN: 67978

Other (OTH) AF: 0.433 AC: 912 AN: 2108

Alfa AF: 0.441 Hom.: 28308

Bravo AF: 0.400

Asia WGS AF: 0.437 AC: 1521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.84
PhyloP100		-0.41
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: rs2425817; hg19: chr20-44895286;