NM_021248.3:c.1663+1923G>C

Variant names:

• chr20-46184665-C-G
• rs6074061
• NM_021248.3:c.1663+1923G>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.1663+1923G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,012 control chromosomes in the GnomAD database, including 5,739 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 0.27 (5739 hom., cov: 31)
• Consequence: CDH22 NM_021248.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH22	NM_021248.3	c.1663+1923G>C		intron_variant	Intron 10 of 11	ENST00000537909.4	NP_067071.1
CDH22	XM_011528994.3	c.1663+1923G>C		intron_variant	Intron 10 of 11		XP_011527296.1
CDH22	XM_047440373.1	c.1424-6468G>C		intron_variant	Intron 8 of 9		XP_047296329.1
CDH22	XM_024451966.2	c.1300+1923G>C		intron_variant	Intron 10 of 11		XP_024307734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH22	ENST00000537909.4	c.1663+1923G>C		intron_variant	Intron 10 of 11	2	NM_021248.3	ENSP00000437790.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41635 AN: 151894 Hom.: 5734 Cov.: 31

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.274 AC: 41647 AN: 152012 Hom.: 5739 Cov.: 31 AF XY: 0.272 AC XY: 20198 AN XY: 74286

African (AFR) AF: 0.266 AC: 11045 AN: 41466

American (AMR) AF: 0.275 AC: 4201 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1072 AN: 3466

East Asian (EAS) AF: 0.162 AC: 840 AN: 5170

South Asian (SAS) AF: 0.311 AC: 1496 AN: 4810

European-Finnish (FIN) AF: 0.269 AC: 2839 AN: 10538

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19219 AN: 67972

Other (OTH) AF: 0.283 AC: 596 AN: 2108

Alfa AF: 0.268 Hom.: 725

Bravo AF: 0.272

Asia WGS AF: 0.253 AC: 883 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.49
PhyloP100		0.29
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: rs6074061; hg19: chr20-44813304;