20-46215836-C-T

Variant names:

• chr20-46215836-C-T
• rs2425786
• NM_021248.3:c.838+990G>A

Variant summary

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

The NM_021248.3(CDH22):​c.838+990G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,072 control chromosomes in the GnomAD database, including 23,559 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 0.52 (23559 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH22	NM_021248.3	c.838+990G>A		intron_variant	Intron 5 of 11	ENST00000537909.4	NP_067071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH22	ENST00000537909.4	c.838+990G>A		intron_variant	Intron 5 of 11	2	NM_021248.3	ENSP00000437790.1
CDH22	ENST00000474438.1	n.706+990G>A		intron_variant	Intron 3 of 4	1

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78612 AN: 151954 Hom.: 23558 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.517 AC: 78634 AN: 152072 Hom.: 23559 Cov.: 32 AF XY: 0.518 AC XY: 38496 AN XY: 74350

African (AFR) AF: 0.196 AC: 8117 AN: 41500

American (AMR) AF: 0.565 AC: 8637 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2108 AN: 3472

East Asian (EAS) AF: 0.452 AC: 2327 AN: 5150

South Asian (SAS) AF: 0.582 AC: 2801 AN: 4816

European-Finnish (FIN) AF: 0.665 AC: 7035 AN: 10586

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45629 AN: 67950

Other (OTH) AF: 0.558 AC: 1179 AN: 2114

Alfa AF: 0.592 Hom.: 10824

Bravo AF: 0.495

Asia WGS AF: 0.516 AC: 1792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.35
PhyloP100		-0.24
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: rs2425786; hg19: chr20-44844475;