rs6017767

chr20-46303290-C-Gchr20-46303290-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021248.3(CDH22):c.-400+4965G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,076 control chromosomes in the GnomAD database, including 12,990 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 (12990 hom., cov: 32)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH22	NM_021248.3	c.-400+4965G>C		intron_variant		ENST00000537909.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH22	ENST00000537909.4	c.-400+4965G>C		intron_variant		2	NM_021248.3	P1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60962 AN: 151958 Hom.: 12995 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.567

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.452

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.406

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

GnomAD4 genome AF: 0.401 AC: 60965 AN: 152076 Hom.: 12990 Cov.: 32 AF XY: 0.404 AC XY: 30013 AN XY: 74328

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.452

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.402

Alfa AF: 0.298 Hom.: 876

Bravo AF: 0.388

Asia WGS AF: 0.419 AC: 1457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.4
Dann	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6017767; hg19: chr20-44931929;