20-46206405-T-G

Variant names:

• chr20-46206405-T-G
• rs1010310
• NM_021248.3:c.1286+3902A>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.1286+3902A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 152,114 control chromosomes in the GnomAD database, including 40,276 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 0.72 (40276 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 8 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]

ENSG00000299003 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021248.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH22	NM_021248.3	MANE Select	c.1286+3902A>C		intron	N/A	NP_067071.1	Q9UJ99

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH22	ENST00000537909.4	TSL:2 MANE Select	c.1286+3902A>C		intron	N/A	ENSP00000437790.1	Q9UJ99
	CDH22	ENST00000946368.1		c.1286+3902A>C		intron	N/A	ENSP00000616427.1
	CDH22	ENST00000946370.1		c.1286+3902A>C		intron	N/A	ENSP00000616429.1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109558 AN: 151996 Hom.: 40243 Cov.: 32

Gnomad AFR AF: 0.836

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.721 AC: 109642 AN: 152114 Hom.: 40276 Cov.: 32 AF XY: 0.716 AC XY: 53206 AN XY: 74360

African (AFR) AF: 0.835 AC: 34661 AN: 41486

American (AMR) AF: 0.640 AC: 9784 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2186 AN: 3464

East Asian (EAS) AF: 0.408 AC: 2109 AN: 5168

South Asian (SAS) AF: 0.616 AC: 2968 AN: 4816

European-Finnish (FIN) AF: 0.739 AC: 7828 AN: 10586

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47758 AN: 67992

Other (OTH) AF: 0.696 AC: 1468 AN: 2110

Alfa AF: 0.698 Hom.: 53559

Bravo AF: 0.716

Asia WGS AF: 0.572 AC: 1991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.1
DANN	Benign	0.53
PhyloP100		-0.0090
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: rs1010310; hg19: chr20-44835044;