chr20-46206405-T-G

Position:

• chr20-46206405-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC124904916 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH22	NM_021248.3	c.1286+3902A>C		intron_variant		ENST00000537909.4	NP_067071.1
LOC124904916	XR_007067612.1	n.384+166T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH22	ENST00000537909.4	c.1286+3902A>C		intron_variant		2	NM_021248.3	ENSP00000437790	P1

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

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.616

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.696

Alfa AF: 0.696 Hom.: 35748

Bravo AF: 0.716

Asia WGS AF: 0.572 AC: 1991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.1
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs1010310; hg19: chr20-44835044;